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Phenylephrine preconditioning of isolated ventricular myocytes involves modulation of KATP channels through activation of survival kinases

By Helen Elizabeth Turrell


Pretreatment with the α1-adrenoceptor agonist phenylephrine has been shown to protect cardiac tissue from a subsequent period of ischaemia. This phenomenon, known as pharmacological preconditioning, decreases infarct size and increases the functional recovery of the intact heart. The role of protein kinases and ATP-sensitive potassium channels (KATP) in phenylephrine preconditioning was investigated in isolated ventricular myocytes using whole cell patch clamp, western blotting, fluorescence imaging and measurement of contractile activity. The role of PKC isoforms was examined using isoform-specific PKC activator and inhibitor peptides.\ud Preconditioning with phenylephrine increased the contractile recovery of isolated ventricular myocytes following simulated ischaemia and reperfusion, and this was also correlated with an improvement in calcium homeostasis during reperfusion. The protective effect of phenylephrine preconditioning on contractile recovery was abolished by inhibition of α1-adrenoceptors, PKC or KATP. We observed a sustained activation of PKCε and δ in response to phenylephrine preconditioning, and identified a protective role for PKCε. PKCδ was required for phenylephrine preconditioning but also increased reperfusion injury. CaMKK, AMPK and p38 MAPK were all required for phenylephrine preconditioning, and activation of AMPK by phenylephrine preconditioning required PKCδ. However, both JNK and ERK appear not to be involved in the protective effect.\ud Inhibition of sarcolemmal KATP channels (sarcKATP) or mitochondrial KATP channels (mitoKATP) prevented preconditioning. Peak sarcKATP current activated by metabolic inhibition was increased following phenylephrine preconditioning and inhibition of PKCδ, AMPK or p38 MAPK was sufficient to prevent the increase in current.\ud Increased sarcKATP current can enhance hyperpolarisation of the resting membrane potential, and may be responsible for the observed decrease in calcium loading and improved contractile recovery of phenylephrine preconditioned ventricular myocytes following ischaemia and reperfusion

Publisher: University of Leicester
Year: 2009
OAI identifier:

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  3. (1996). A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K + channels.
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  5. (2005). A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II).
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  7. (1997). A truncated HIV-1 Tat protein basic domain rapidly translocates through the plasma membrane and accumulates in the cell nucleus.
  8. (1997). absence of the sulphonylurea receptor.
  9. (2001). Acetylcholine, bradykinin, opioids, and phenylephrine, but not adenosine, trigger preconditioning by generating free radicals and opening mitochondrial KATP channels.
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  12. (1998). Activation of alpha1-adrenergic receptor during Ca 2+ pre-conditioning elicits strong protection against Ca 2+ overload injury via protein kinase C signaling pathway.
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  14. (2007). Activation of alpha1B-adrenoceptors alleviates ischemia/reperfusion injury by limitation of mitochondrial Ca 2+ overload in cardiomyocytes.
  15. (1994). Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs.
  16. (2002). Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress.
  17. (2005). Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoforms.
  18. (1998). Activation of mitogen-activated protein kinases (p38-MAPKs, SAPKs/JNKs and ERKs) by the G-protein-coupled receptor agonist phenylephrine in the perfused rat heart.
  19. (1995). Activation of mitogen-activated protein kinases and activator protein-1 in myocardial infarction in rats.
  20. (2001). Activation of Na protein kinases in the ischemic and ischemic-reperfused rat myocardium.
  21. (2001). Activation of p38 MAPK induced by a multi-cycle ischaemic preconditioning protocol is associated with attenuated p38 MAPK activity during sustained ischaemia and reperfusion.
  22. (1999). Activation of the JNK pathway is important for cardiomyocyte death in response to simulated ischemia.
  23. (2003). Additive protection of the ischemic heart ex vivo by combined treatment with delta-protein kinase C inhibitor and epsilon-protein kinase C activator.
  24. (2003). Adenine nucleotide translocase mediates the KATP-channel-openers-induced proton and potassium flux to the mitochondrial matrix.
  25. (2005). Adenosine 5'-monophosphate-activated protein kinase and p38 mitogen-activated protein kinase participate in the stimulation of glucose uptake by dinitrophenol in adult cardiomyocytes.
  26. (1995). Adenosine triphosphate-dependent K currents activated by metabolic inhibition in rat ventricular myocytes differ from those elicited by the channel opener rilmakalim.
  27. (1999). Adenosine-induced activation of ATP-sensitive
  28. (2001). Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels.
  29. (1994). alpha1-adrenergic agonists precondition rabbit ischemic myocardium independent of adenosine by direct activation of protein kinase
  30. (1995). Alpha1-adrenergic receptor agonist-induced preconditioning in isolated working rat hearts.
  31. (2007). alpha1-adrenergic receptors activate AMP-activated protein kinase in rat hearts.
  32. (1994). Alpha1-adrenoceptor activation mediates the infarct size-limiting effect of ischemic preconditioning through augmentation of 5'-nucleotidase activity.
  33. (1987). Alpha1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca 2+ in smooth muscle.
  34. (1999). Alpha1-adrenoceptor subtypes.
  35. (2001). AlphaB crystallin translocation and phosphorylation: signal transduction pathways and preconditioning in the isolated rat heart.
  36. (1993). Alterations in electrical activity and membrane currents induced by intracellular oxygen-derived free radical stress in guinea pig ventricular myocytes.
  37. (2005). AMP-activated protein kinase activates p38 mitogen-activated protein kinase by increasing recruitment
  38. (2007). AMP-activated protein kinase in metabolic control and insulin signaling.
  39. (2007). AMP-activated protein kinase in the heart: role during health and disease.
  40. (2007). AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive
  41. (1997). Anoxia-induced activation of ATP-sensitive K + channels in guinea pig ventricular cells and its modulation by glycolysis.
  42. (1999). Antioxidative properties of pyruvate and protection of the ischemic rat heart during cardioplegia.
  43. (1999). Apoptosis in myocardial ischemia-reperfusion.
  44. (1996). Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats.
  45. (2008). Arrhythmogenic substrates in myocardial infarct.
  46. (2001). ATP consumption by uncoupled mitochondria activates sarcolemmal KATP channels in cardiac myocytes.
  47. (2001). ATP sensitive K + channel may be involved in the protective effects of preconditioning in isolated guinea pig cardiomyocytes.
  48. (1983). ATP-regulated K + channels in cardiac muscle.
  49. (1991). ATP-sensitive
  50. (1992). ATP-sensitive K + channels and cellular K + loss in hypoxic and ischaemic mammalian ventricle.
  51. (1991). ATP-sensitive potassium channel modulation of the guinea pig ventricular action potential and contraction.
  52. (2003). ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase
  53. (2005). ATPsensitive K + channel channel/enzyme multimer: metabolic gating in the heart.
  54. (2004). Biodistribution of intracellularly acting peptides conjugated reversibly to Tat.
  55. (1992). Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs.
  56. (1992). Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate.
  57. (1996). Bradykinin protects against infarction but does not mediate ischemic preconditioning in the isolated rat heart.
  58. (2000). c-Jun NH(2)-terminal kinase inhibits targeting of the protein phosphatase calcineurin to NFATc1.
  59. (1995). C2 region-derived peptides inhibit translocation and function of beta protein kinase C in vivo.
  60. (2003). Calcium and apoptosis: facts and hypotheses.
  61. (2008). Calcium cycling and signaling in cardiac myocytes.
  62. (1996). Calcium preconditioning elicits strong protection against ischemic injury via protein kinase C signaling pathway.
  63. (2007). Calmodulin kinase II inhibition enhances ischemic preconditioning by augmenting ATP-sensitive K + current.
  64. (1993). Cardiac alpha1-adrenoceptors: an overview.
  65. (2002). Cardiac excitation-contraction coupling.
  66. (1998). Cardiac muscle cell hypertrophy and apoptosis induced by distinct members of the p38 mitogen-activated protein kinase family.
  67. (1993). Cardiac stress protein elevation 24 hours after brief ischemia or heat stress is associated with resistance to myocardial infarction.
  68. (2000). Cardioprotection with kappa-opioid receptor stimulation is associated with a slowing of cross-bridge cycling.
  69. (1995). Cardioprotection with the KATP opener cromakalim is not correlated with ischemic myocardial action potential duration.
  70. (1997). Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K +
  71. (2003). Cardioprotective effect of diazoxide is mediated by activation of sarcolemmal but not mitochondrial ATP-sensitive potassium channels in mice.
  72. (1999). Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts.
  73. (1993). Catecholamines can induce adenosine receptor-mediated protection of the myocardium but do not participate in ischemic preconditioning in the rabbit.
  74. (1997). Comparison of in vitro preconditioning responses of isolated pig and rabbit cardiomyocytes: effects of a protein phosphatase inhibitor,
  75. (2003). Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade.
  76. (1960). Complexes of cytochrome c oxidase with cyanide and carbon monoxide.
  77. (2005). Connexin 43 in cardiomyocyte mitochondria and its increase by ischemic preconditioning.
  78. (1983). Contraction band necrosis and irreversible myocardial injury.
  79. (1999). Contribution of alpha-adrenergic and beta-adrenergic stimulation to ischemia-induced glucose transporter (GLUT) 4 and GLUT1 translocation in the isolated perfused rat heart.
  80. (1972). Cooperation within actin filament in vertebrate skeletal muscle.
  81. (1998). Coordinate interaction between ATP-sensitive K modulates ischemic preconditioning.
  82. (2008). Coronary Heart Disease Statistics.
  83. (2002). Coupling of cell energetics with membrane metabolic sensing. Integrative signaling through creatine kinase phosphotransfer disrupted by M-CK gene knock-out.
  84. (2002). Creatine kinase is physically associated with the cardiac ATP-sensitive K + channel in vivo.
  85. (1998). Creatine kinase: an enzyme with a central role in cellular energy metabolism.
  86. Delayed effects of sublethal ischemia on the acquisition of tolerance to ischemia.
  87. (2008). Delta protein kinase C interacts with the d subunit of the F1F0 ATPase in neonatal cardiac myocytes exposed to hypoxia or phorbol ester. Implications for F1F0 ATPase regulation.
  88. (2005). DeltaPKC-mediated activation of epsilonPKC in ethanolinduced cardiac protection from ischemia.
  89. (1998). Demonstration of a Ca Vanden
  90. (1989). Depression of heart sarcolemmal Ca 2+ -pump activity by oxygen free radicals.
  91. (2008). Diastolic calcium is elevated in metabolic recovery of cardiomyocytes expressing elevated levels of the Na exchanger.
  92. Diazoxide acts more as a PKC-epsilon activator, and indirectly activates the mitochondrial KATP channel conferring cardioprotection against hypoxic injury.
  93. (2004). Diazoxide causes early activation of cardiac sarcolemmal KATP channels during metabolic inhibition by an indirect mechanism.
  94. (1997). Different preconditioning stimuli invoke disparate electromechanical and energetic responses to global ischemia in rat hearts.
  95. (2001). Differential activation of extracellular signal regulated kinase isoforms in preconditioning and opioid-induced cardioprotection.
  96. (2001). Differential activation of mitogenactivated protein kinase cascades and apoptosis by protein kinase C epsilon and delta in neonatal rat ventricular myocytes.
  97. (2002). Differential effect of ischemic and pharmacological preconditioning on PKC isoform translocation in adult rat cardiac myocytes.
  98. (2000). Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning.
  99. (2002). Dinitrophenol pretreatment of rat ventricular myocytes protects against damage by metabolic inhibition and reperfusion.
  100. (2002). Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes.
  101. (2006). Dissecting the role of 5'-AMP for allosteric stimulation, activation, and deactivation of AMP-activated protein kinase.
  102. (2002). Dissociation of stress-activated protein kinase (p38-MAPK and JNKs) phosphorylation from the protective effect of preconditioning in vivo.
  103. (2001). Distinct myoprotective roles of cardiac sarcolemmal and mitochondrial KATP channels during metabolic inhibition and recovery.
  104. (2004). Distinctive activation mechanisms and functions for protein kinase
  105. (2005). Dual mechanisms regulating AMPK kinase action in the ischemic heart.
  106. (1998). Dual regulation of the AMP-activated protein kinase provides a novel mechanism for the control of creatine kinase in skeletal muscle.
  107. (1997). Early and delayed preconditioning: differential mechanisms and additive protection.
  108. (1992). Effect of alpha-adrenergic stimulation on activation of protein kinase C and phosphorylation of proteins in intact rabbit hearts.
  109. (1991). Effect of inhibition of the mitochondrial ATPase on net myocardial ATP in total ischemia.
  110. (1994). Effect of ischemic preconditioning on ischemia-induced contractile failure and accumulation of extracellular
  111. (2002). Effect of metabolic inhibition on glimepiride block of native and cloned cardiac sarcolemmal KATP channels.
  112. (1977). Effects of acidosis and ischemia on contractility and intracellular pH of rat heart.
  113. (1998). Effects of alpha1-adrenergic stimulation on L-type Ca 2+ current in rat ventricular myocytes.
  114. (1991). Effects of ATP-sensitive K + channel blockers on the action potential shortening in hypoxic and ischaemic myocardium.
  115. (1992). Effects of oxygen free radicals on isolated cardiac myocytes from guinea-pig ventricle: electrophysiological studies.
  116. (1978). Effects of pH on the myofilaments and the sarcoplasmic reticulum of skinned cells from cardiace and skeletal muscles.
  117. (1992). Effects of simulated ischemia and reperfusion on the sarcoplasmic reticulum of digitonin-lysed cardiomyocytes.
  118. (1998). Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart.
  119. (2006). Endogenous adenosine protects preconditioned heart during early minutes of reperfusion by activating Akt.
  120. (1994). Endothelin-1 and fibroblast growth factors stimulate the mitogen-activated protein kinase signaling cascade in cardiac myocytes. The potential role of the cascade in the integration of two signaling pathways leading to myocyte hypertrophy.
  121. (2009). Endothelin-I and angiotensin II inhibit arterial voltage-gated K+ channels through different protein kinase C isoenzymes.
  122. (1986). Energy dependence of contraction band formation in perfused hearts and isolated adult myocytes.
  123. (2004). ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions.
  124. (2008). Essential role of lipid raft in ischemic preconditioning.
  125. (2000). Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development.
  126. (1994). Evidence that translocation of protein kinase C is a key event during ischemic preconditioning of rabbit myocardium.
  127. (2005). Genetic inhibition or activation of JNK1/2 protects the myocardium from ischemiareperfusion-induced cell death in vivo.
  128. (1994). Glucose transport and phosphorylation in single cardiac myocytes: rate-limiting steps in glucose metabolism.
  129. (2002). H2O2-induced Ca 2+ overload in NRVM involves ERK1/2 MAP kinases: role for an NHE-1-dependent pathway.
  130. (1997). Halothane protects cardiomyocytes against reoxygenation-induced hypercontracture.
  131. (2008). Heart mitochondria: gates of life and death.
  132. (1998). HMR 1883, a novel cardioselective inhibitor of the ATP-sensitive potassium channel. Part I: effects on cardiomyocytes, coronary flow and pancreatic beta-cells.
  133. (1983). Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway.
  134. (2002). Hypoxia and persistent sodium current.
  135. (2004). Hypoxia regulates the adenosine transporter, mENT1, in the murine cardiomyocyte cell line,
  136. (2004). Hypoxia-induced preconditioning in adult stimulated cardiomyocytes is mediated by the opening and trafficking of sarcolemmal KATP channels.
  137. (1993). Hypoxic preconditioning attenuates stunning caused by repeated coronary artery occlusions in dog heart.
  138. (2005). Identification and pharmacological characterization of sarcolemmal ATP-sensitive potassium channels in the murine atrial HL-1 cell line.
  139. (1991). Identification of intracellular receptor proteins for activated protein kinase
  140. (1997). Implication of protein kinase C-alpha, delta, and epsilon isoforms in ischemic preconditioning in perfused rat hearts.
  141. (2007). Induction of apoptosis is driven by nuclear retention of protein kinase
  142. (1997). Infarct size-reducing effect of ischemic preconditioning is related to alpha1badrenoceptors but not to alpha1a-adrenoceptors in rabbits.
  143. (2001). Inhibition of c-Jun N-terminal kinase 1, but not c-Jun N-terminal kinase 2, suppresses apoptosis induced by ischemia/reoxygenation in rat cardiac myocytes.
  144. (2003). Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo.
  145. (2005). Inhibition of Na channel by glibenclamide in Guinea pig ventricular myocytes.
  146. (1999). Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion.
  147. (1984). Inhibition of the activation and troponin calcium binding of dog cardiac myofibrils by acidic pH.
  148. (1990). Inorganic phosphate inhibits contractility and ATPase activity in skinned fibers from human myocardium.
  149. (2000). Integrative analysis of calcium cycling in cardiac muscle.
  150. (2008). Interaction of alpha1-adrenoceptor subtypes with different G proteins induces opposite effects on cardiac L-type Ca 2+ channel.
  151. (1995). Ischaemic preconditioning in a model of global ischaemia: infarct size limitation, but no reduction of stunning.
  152. (1995). Ischaemic preconditioning is protein kinase C dependent but not through stimulation of alpha adrenergic or adenosine receptors in the isolated rat heart.
  153. (1993). Ischaemic preconditioning--time course of renewal in the pig.
  154. (2001). Ischemic and anesthetic preconditioning reduces cytosolic [Ca 2+ ] and improves Ca 2+ responses in intact hearts.
  155. (2001). Ischemic and pharmacological preconditioning
  156. (1977). Ischemic contracture of the myocardium: mechanisms and prevention.
  157. (2004). Ischemic preconditioning activates AMPK in a PKC-dependent manner and induces GLUT4 upregulation in the late phase of cardioprotection.
  158. (2004). Ischemic preconditioning exaggerates cardiac damage in PKC-delta null mice.
  159. (2000). Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function.
  160. (1997). Ischemic preconditioning induces selective translocation of protein kinase C isoforms epsilon and eta in the heart of conscious rabbits without subcellular redistribution of total protein kinase C activity.
  161. (2007). Ischemic preconditioning involves dual cardio-protective axes with p38MAPK as upstream target.
  162. (1997). Ischemic preconditioning of human myocardium: protein kinase C mediates a permissive role for alpha1-adrenoceptors.
  163. (2008). Ischemic preconditioning of the whole heart confers protection on subsequently isolated ventricular myocytes.
  164. Ischemic preconditioning preserves connexin 43 phosphorylation during sustained ischemia in pig hearts in vivo.
  165. (2000). Ischemic preconditioning prevents I/R-induced alterations in SR calcium-calmodulin protein kinase II.
  166. (1998). Ischemic preconditioning translocates PKC-delta and -epsilon, which mediate functional protection in isolated rat heart.
  167. (2000). Ischemic preconditioning: from adenosine receptor to KATP channel.
  168. (2007). Ischemic preconditioning: protection against myocardial necrosis and apoptosis.
  169. (2007). Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation.
  170. (2008). JNK signaling in apoptosis.
  171. (2005). KATP channels and preconditioning: a re-examination of the role of mitochondrial KATP channels and an overview of alternative mechanisms.
  172. (2003). Knockout of Kir6.2 negates ischemic preconditioning-induced protection of myocardial energetics.
  173. (2007). KSR and CNK: two scaffolds regulating RAS-mediated RAF activation.
  174. (1985). Local release of myocardial norepinephrine during acute ischemia: an experimental study in the isolated perfused rat heart.
  175. (1993). Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment.
  176. (2001). Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation.
  177. (2006). Mammalian TAK1 activates Snf1 protein kinase in yeast and phosphorylates AMP-activated protein kinase in vitro.
  178. (1989). Mechanism for depression of heart sarcolemmal Ca 2+ -pump by oxygen free radicals.
  179. (1990). Mechanism of myocardial "stunning".
  180. (1995). Mechanisms of ischemic preconditioning in rat hearts. Involvement of alpha1B-adrenoceptors, pertussis toxin-sensitive G proteins, and protein kinase
  181. (1998). Mechanisms of pH preservation during global ischemia in preconditioned rat heart: roles for PKC and NHE.
  182. (2005). Mechanisms of xenon- and isoflurane-induced preconditioning - a potential link to the cytoskeleton via the MAPKAPK2/HSP27 pathway.
  183. (1998). Mitochondrial ATP-dependent potassium channels: novel effectors of cardioprotection?
  184. (2005). Mitochondrial Ca 2+ -activated K + channels in cardiac myocytes: a mechanism of the cardioprotective effect and modulation by protein kinase A.
  185. (1995). Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion.
  186. (2004). Mitochondrial permeability transition pore opening during myocardial reperfusion--a target for cardioprotection.
  187. (2006). Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K + channel copurify and coreconstitute to form a functioning signaling module in proteoliposomes.
  188. (2007). Mitochondrial protein kinase Cepsilon (PKCepsilon): emerging role in cardiac protection from ischaemic damage.
  189. (2007). Modeling transmural heterogeneity of KATP current in rabbit ventricular myocytes.
  190. (2005). Modest actomyosin energy conservation increases myocardial postischemic function.
  191. (1999). Modulation of recombinant human cardiac L-type Ca 2+ channel alpha1C subunits by redox agents and hypoxia.
  192. (1998). Modulation of rigor and myosin ATPase activity in rat cardiomyocytes.
  193. (1999). Molecular and cellular mechanisms of myocardial stunning.
  194. (2000). Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels.
  195. (2000). Molecular composition of mitochondrial ATP-sensitive potassium channels probed by viral Kir gene transfer.
  196. (1999). Molecular mechanisms of myocardial remodeling.
  197. (2004). Multiprotein complex containing succinate dehydrogenase confers mitochondrial ATP-sensitive K + channel activity.
  198. (2003). Myocardial adenosine does not correlate with the protection mediated by ischaemic or pharmacological preconditioning in rat heart.
  199. (1987). Myocardial contractile function during ischemia and hypoxia.
  200. (2007). Myocardial protection in man--from research concept to clinical practice.
  201. (1991). Myocardial protection is lost before contractile function recovers from ischemic preconditioning.
  202. (2001). Na ischemia, reperfusion and preconditioning.
  203. (2002). No ischemic preconditioning in heterozygous connexin43-deficient mice.
  204. (1997). Nuclear accumulation of NFAT4 opposed by the JNK signal transduction pathway.
  205. (1989). Nucleotide modulation of the activity of rat heart ATP-sensitive K + channels in isolated membrane patches.
  206. (1993). On the mechanism of inhibition of KATP channels by glibenclamide in rat ventricular myocytes.
  207. (2002). Opening of mitochondrial KATP channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning.
  208. (2000). Opening of the mitochondrial permeability transition pore causes matrix expansion and outer membrane rupture in Fas-mediated hepatic apoptosis in mice.
  209. Opposing cardioprotective actions and parallel hypertrophic effects of delta PKC and epsilon PKC.
  210. (1996). Origin of concurrent ATPase activities in skinned cardiac trabeculae from rat.
  211. (2005). Overexpression of mitogen-activated protein kinase kinase 6 in the heart improves functional recovery from ischemia in vitro and protects against myocardial infarction in vivo.
  212. (2001). Overexpression of Na adult rat myocytes.
  213. (1997). Oxygen radicals can induce preconditioning in rabbit hearts.
  214. (1997). Oxygen radicals released during ischemic preconditioning contribute to cardioprotection in the rabbit myocardium.
  215. (2005). Oxygen, oxidative stress, hypoxia, and heart failure.
  216. (2004). p38 and JNK have distinct regulatory functions on the development of apoptosis during simulated ischaemia and reperfusion in neonatal cardiomyocytes.
  217. (1996). Paradoxical effect of ischemic preconditioning on ischemic contracture? NMR studies of energy metabolism and intracellular pH in the rat heart.
  218. (2004). Pharmacological activation of plasma-membrane KATP channels reduces reoxygenation-induced Ca 2+ overload in cardiac myocytes via modulation of the diastolic membrane potential.
  219. (2002). Pharmacological and ischemic preconditioning of the human myocardium: mitoKATP channels are upstream and p38MAPK is downstream of PKC.
  220. (1999). Pharmacological plasticity of cardiac ATP-sensitive potassium channels toward diazoxide revealed by ADP.
  221. (1998). Phenylephrine-induced stimulation of exchange in rat ventricular myocytes.
  222. (1994). Phospholipase C-gamma 1 binding to intracellular receptors for activated protein kinase
  223. (1997). Phosphorylation of tyrosine 182 of p38 mitogen-activated protein kinase correlates with the protection of preconditioning in the rabbit heart.
  224. (2003). Physiological and pathophysiological roles of ATP-sensitive
  225. (2002). PI3 kinase and not p42/p44 appears to be implicated in the protection conferred by ischemic preconditioning.
  226. (2002). PKC-delta inhibition does not block preconditioning-induced preservation in mitochondrial ATP synthesis and infarct size reduction in rats.
  227. (1999). PKC-dependent activation of p44/p42 MAPKs during myocardial ischemia-reperfusion in conscious rabbits.
  228. (1999). PKC-dependent activation of p46/p54 JNKs during ischemic preconditioning in conscious rabbits.
  229. (2004). PKC-epsilon is upstream and PKC-alpha is downstream of mitoKATP channels in the signal transduction pathway of ischemic preconditioning of human myocardium.
  230. (2008). PKCbeta modulates ischemiareperfusion injury in the heart.
  231. Possible mechanism of cardioprotection.
  232. (2004). Potassium channel openers are uncoupling protonophores: implication in cardioprotection.
  233. (2003). potassium channel subunits in isolated ventricular myocytes.
  234. (1993). Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha1-adrenergic mechanism.
  235. (2007). Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore.
  236. (2005). Preconditioning by isoflurane induces lasting sensitization of the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel by a protein kinase C-delta-mediated mechanism.
  237. (1992). Preconditioning does not attenuate myocardial stunning.
  238. (2007). Preconditioning in humans.
  239. (1995). Preconditioning of isolated rat heart is mediated by protein kinase
  240. (1998). Preconditioning prevents myocardial stunning after cardiac transplantation.
  241. (2004). Preconditioning protects by inhibiting the mitochondrial permeability transition.
  242. (1994). Preconditioning protects ischemic rabbit heart by protein kinase C activation.
  243. (1995). Preconditioning reduces infarct size but accelerates time to ventricular fibrillation in ischemic pig heart.
  244. (2003). Preconditioning the myocardium: from cellular physiology to clinical cardiology.
  245. (1986). Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
  246. (2006). Preconditioning, postconditioning and their application to clinical cardiology.
  247. (2009). Presence of connexin 43 in subsarcolemmal, but not in interfibrillar cardiomyocyte mitochondria.
  248. (1980). Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction.
  249. (2000). Principles of physiology, 3rd edn,
  250. (2000). Pro-apoptotic cascade activates BID, which oligomerizes BAK or BAX into pores that result in the release of cytochrome c.
  251. (1991). Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.
  252. (2004). Protection from the effects of metabolic inhibition and reperfusion in contracting isolated ventricular myocytes via protein kinase C activation.
  253. (1997). Protection of ischemic preconditioning is dependent upon a critical timing sequence of protein kinase C activation.
  254. (1994). Protection of myocardium by transient, preischemic administration of phenylephrine in the rabbit.
  255. (1990). Protective effects of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products.
  256. (2003). Protective effects of SEA0400, a novel and selective inhibitor of the exchanger, on myocardial ischemia-reperfusion injuries.
  257. (2004). Protein kinase activation and myocardial ischemia/reperfusion injury.
  258. (1996). Protein kinase C activates ATP-sensitive K + current in human and rabbit ventricular myocytes.
  259. (1987). Protein kinase C contains a pseudosubstrate prototope in its regulatory domain.
  260. (2005). Protein kinase C delta and epsilon mediate positive inotropy in adult ventricular myocytes.
  261. (2001). Protein kinase C isoform-dependent modulation of ATP-sensitive K + channels during reoxygenation in guinea-pig ventricular myocytes.
  262. (2006). Protein kinase C regulatory domains: the art of decoding many different signals in membranes.
  263. (2004). Protein kinase C-epsilon primes the cardiac sarcolemmal adenosine triphosphate-sensitive potassium channel to modulation by isoflurane.
  264. (1996). Protein kinase C-induced changes in the stoichiometry of ATP binding activate cardiac ATP-sensitive K + channels. A possible mechanistic link to ischemic preconditioning.
  265. (2007). Protein kinase Cdelta and apoptosis.
  266. (2007). Protein kinase Cepsilon (PKCepsilon) and Src control PKCdelta activation loop phosphorylation in cardiomyocytes.
  267. (2003). Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria.
  268. (2006). Protein kinase Cepsilon interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning.
  269. (1994). Pyruvate increases threshold for preconditioning in globally ischemic rat hearts.
  270. (1998). Recombinant cardiac ATP-sensitive K+ channel subunits confer resistance to chemical hypoxia-reoxygenation injury.
  271. (1992). Reconstitution and partial purification of the glibenclamide-sensitive, ATP-dependent K + channel from rat liver and beef heart mitochondria.
  272. (1995). Recurrent ischemia in the canine heart causes recurrent bursts of free radical production that have a cumulative effect on contractile function. A pathophysiological basis for chronic myocardial "stunning".
  273. (1986). Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles.
  274. (2006). Redox regulation of cardiac calcium channels and transporters.
  275. (2007). Redox regulation of ischemic preconditioning is mediated by the differential activation of caveolins and their association with eNOS and GLUT-4. Am.J.Physiol.Heart Circ.Physiol.
  276. (2005). Reduced effectiveness of HMR 1098 in blocking cardiac sarcolemmal KATP channels during metabolic stress.
  277. (1975). Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs.
  278. (2009). Regulation of ATP-sensitive K + channels by caveolin-enriched microdomains in cardiac myocytes.
  279. (2003). Regulation of MAP kinase signaling modules by scaffold proteins in mammals.
  280. (2008). Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease.
  281. (1997). Regulation of phospholipases C and D in rat ventricular myocytes: stimulation by endothelin-1, bradykinin and phenylephrine.
  282. (2009). Remodelling of cardiac repolarization: how homeostatic responses can lead to arrhythmogenesis.
  283. (2003). Reoxygenation-induced rigor-type contracture.
  284. (1994). Reperfusion injury induces apoptosis in rabbit cardiomyocytes.
  285. (2001). Responses of GLUT4-deficient hearts to ischemia underscore the importance of glycolysis.
  286. (2003). Resting membrane potential regulates Na overload during hypoxia-reoxygenation in rat ventricular myocytes.
  287. (1999). Reversal of permeability transition during recovery of hearts from ischemia and its enhancement by pyruvate.
  288. (1992). Reversible exposure of the pseudosubstrate domain of protein kinase C by phosphatidylserine and diacylglycerol.
  289. (2008). Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease.
  290. (2004). Role of apoptosis in reperfusion injury.
  291. (2004). Role of connexin 43 in ischemic preconditioning does not involve intercellular communication through gap junctions.
  292. (2001). Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart.
  293. (2005). Role of mitochondrial re-energization and Ca 2+ influx in reperfusion injury of metabolically inhibited cardiac myocytes.
  294. (1999). Role of Na , and adenine nucleotides under normal and simulated ischemic conditions.
  295. (1999). Role of protein kinase C in mitochondrial KATP channel-mediated protection against Ca 2+ overload injury in rat myocardium.
  296. (2002). Role of sarcolemmal KATP channels in cardioprotection against ischemia/reperfusion injury in mice.
  297. (2003). Role of the cardiac Na exchanger during ischemia and reperfusion.
  298. (2001). Role of the reverse mode of the Na exchanger in reoxygenation-induced cardiomyocyte injury.
  299. (2000). SAPKs regulation of ischemic preconditioning.
  300. (2002). Sarcolemmal and mitochondrial KATP channels and myocardial ischemic preconditioning.
  301. (2001). Sarcolemmal and mitochondrial KATP channels mediate cardioprotection in chronically hypoxic hearts.
  302. (1999). Sarcolemmal versus mitochondrial ATP-sensitive K + channels and myocardial preconditioning.
  303. Selective interaction of JNK protein kinase isoforms with transcription factors.
  304. (2005). Signal transduction mechanisms involved in cardiac preconditioning: role of Ras-GTPase, Ca 2+ /calmodulin-dependent protein kinase II and epidermal growth factor receptor.
  305. (2008). Simplified apoptotic cascades.
  306. (1996). Simulation of action potentials from metabolically impaired cardiac myocytes.
  307. (1999). Sodium regulation during ischemia versus reperfusion and its role in injury.
  308. Src family kinase and adenosine differentially regulate multiple MAP kinases in ischemic myocardium: modulation of MAP kinases activation by ischemic preconditioning.
  309. (2003). Stable transfection of UCP1 confers resistance to hypoxia/reoxygenation in a heart-derived cell line.
  310. (1996). Stimulation of c-Jun kinase and mitogen-activated protein kinase by ischemia and reperfusion in the perfused rat heart.
  311. (1996). Stimulation of the stress-activated mitogen-activated protein kinase subfamilies in perfused heart. p38/RK mitogen-activated protein kinases and c-Jun N-terminal kinases are activated by ischemia/reperfusion.
  312. (2004). Stress-activated MAP kinases in cardiac remodeling and heart failure; new insights from transgenic studies.
  313. (2001). Stress-activated protein kinase phosphorylation during cardioprotection in the ischemic myocardium.
  314. (1985). Structural and functional properties of adult rat heart myocytes lysed with digitonin.
  315. (2008). Structural basis of protein kinase C isoform function.
  316. (2006). Studying ischemic preconditioning in isolated cardiomyocyte models.
  317. (1991). Sulfonylureas, ATP-sensitive K + channels, and cellular K + loss during hypoxia, ischemia, and metabolic inhibition in mammalian ventricle.
  318. (2004). SUR2A C-terminal fragments reduce KATP currents and ischaemic tolerance of rat cardiac myocytes.
  319. (1999). Sustained in vivo cardiac protection by a rationally designed peptide that causes epsilon protein kinase C translocation.
  320. (1996). Synergistic modulation of ATP-sensitive K + currents by protein kinase C and adenosine. Implications for ischemic preconditioning.
  321. (2008). t-Tubules and sarcoplasmic reticulum function in cardiac ventricular myocytes.
  322. (2008). Targeting p38-MAPK in the ischaemic heart: kill or cure?
  323. (2007). Temperature preconditioning of isolated rat hearts--a potent cardioprotective mechanism involving a reduction in oxidative stress and inhibition of the mitochondrial permeability transition pore.
  324. (2004). Testosterone induces cytoprotection by activating ATP-sensitive K + channels in the cardiac mitochondrial inner membrane.
  325. (2001). The actin cytoskeleton response to oxidants: from small heat shock protein phosphorylation to changes in the redox state of actin itself.
  326. (2004). The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore.
  327. (2004). The AMP-activated protein kinase cascade--a unifying system for energy control.
  328. (2008). The cardiac persistent sodium current: an appealing therapeutic target?
  329. (2009). The divergent roles of protein kinase C epsilon and delta in simulated ischaemiareperfusion injury in human myocardium.
  330. (1986). The effects of inorganic phosphate and creatine phosphate on force production in skinned muscles from rat ventricle.
  331. (2002). The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration.
  332. (1989). The effects of metabolic inhibition on intracellular calcium and pH in isolated rat ventricular cells.
  333. (2000). The epsilon subtype of protein kinase C is required for cardiomyocyte connexin-43 phosphorylation.
  334. (1998). The expression of constitutively active isotypes of protein kinase C to investigate preconditioning.
  335. (2006). The extracellular signal-regulated kinase: multiple substrates regulate diverse cellular functions.
  336. (2004). The first minutes of reperfusion: a window of opportunity for cardioprotection.
  337. (1999). The JIP group of mitogenactivated protein kinase scaffold proteins.
  338. (2000). The KATP channel blocker HMR 1883 does not abolish the benefit of ischemic preconditioning on myocardial infarct mass in anesthetized rabbits.
  339. (2001). The KATP channel opener diazoxide protects cardiac myocytes during metabolic inhibition without causing mitochondrial depolarization or flavoprotein oxidation.
  340. (2006). The mechanism by which the mitochondrial ATP-sensitive K + channel opening and H2O2 inhibit the mitochondrial permeability transition.
  341. (1989). The mechanism of early contractile failure of isolated rat ventricular myocytes subjected to complete metabolic inhibition.
  342. (2009). The mitochondrial permeability transition pore as a target for preconditioning and postconditioning. Basic Res.Cardiol.
  343. (2000). The p38 MAPK inhibitor, SB203580, abrogates ischaemic preconditioning in rat heart but timing of administration is critical.
  344. (2002). The permeability transition pore complex: another view.
  345. (2007). The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic.
  346. (1990). The regulation of ATP-sensitive K + channel activity in intact and permeabilized rat ventricular myocytes.
  347. (2005). The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning.
  348. (1990). The role of ATP in energy-deprivation contractures in unloaded rat ventricular myocytes.
  349. (2000). The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes.
  350. (2008). The role of the Na dynamics in ventricular myocytes.
  351. (2006). The sarcoplasmic reticulum as the primary target of reperfusion protection.
  352. (1997). Tissue-specific pattern of stress kinase activation in ischemic/reperfused heart and kidney.
  353. (2002). Troponin I serines 43/45 and regulation of cardiac myofilament function.
  354. (2003). Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes.
  355. (2007). Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death.
  356. (2007). World Health Organisation

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