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An investigation of the properties of large-conductance Ca^2+-activated K^+ channels of rat arterial smooth muscle and their modulation by vasoconstrictors

By Anna Sowerby


Large-conductance Ca^2+ -activated K^+ (BKCa) channels play an important role in the regulation of vascular tone. They are activated by membrane depolarization and\ud increases in local Ca^2+ concentration ([Ca^2+]). Their location in the plasma membrane allows them to be activated by transient releases of Ca^2+ from ryanodine receptors (RyR) in the sarcoplasmic reticulum, termed Ca^2+ sparks, leading to the efflux of K^+ known as a spontaneous transient outward current (STOC). Activation of BKCa channels in this manner provides a negative feedback mechanism to regulate vasoconstriction by hyperpolarizing the cell membrane and so reducing Ca^2+ influx through L-type voltage dependent Ca2+ channels. In this thesis I have investigated the relationship between [Ca^2+]i and membrane potential using inside-out patches excised from smooth muscle cells isolated from rat mesenteric artery. Whole-cell BKCa currents in these cells were also investigated both in the form of STOCs and by using voltage pulses to activate BKCa channels. The effects of the vasoconstrictors endothelin-1 (ET- 1) and angiotensin II (Ang II) on both pulse-induced BKCa currents and STOC amplitude and frequency were investigated. Single BKCa channels with a slope conductance of 189 pA were recorded and their activation was shown to be dependent on [Ca^2+]i and membrane potential. Membrane depolarization also increased BKCa whole-cell current and the frequency and amplitude of STOCs. ET-1 and Ang II were found to inhibit pulse-induced BKCa currents and this effect of ET-1 could be inhibited using a peptide PKC inhibitor. ET-1 and Ang II also caused a decrease in both STOC amplitude and frequency, although the decrease in frequency may be the result of the reduction in amplitude. Finally, 1, 2-dioctanoyl-sn-glycerol (DOG), an analogue of the endogenous PKC activator diacylglycerol (DAG), was seen to inhibit both BKCa whole-cell and single channel currents, possibly due to direct inhibition of BKCa channels

Publisher: University of Leicester
Year: 2009
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  1. (1996). A calcium switch for the functional coupling between α (hslo) and β subunits (KV, caβ) of maxi K channels.
  2. (2001). A molecular switch for specific stimulation of the BKCa channel by cGMP and cAMP kinase.
  3. (2000). A neuronal beta subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin.
  4. (1997). A novel calcium-sensing domain in the BK channel.
  5. (1988). A novel potent vasoconstrictor peptide produced by vascular endothelial cells.
  6. (2006). A TRPC-like non-selective cation current activated by α1-adrenoceptors in rat mesenteric artery smooth muscle cells.
  7. (1991). Accounting for the ca(2+)-dependent kinetics of single large-conductance ca(2+)-activated K+ channels in rat skeletal muscle.
  8. (2005). Activation of chloride currents in murine portal vein smooth muscle cells by membrane depolarization involves intracellular calcium release.
  9. (1997). Activators of protein kinase C decrease Ca2+ spark frequency in smooth muscle cells from cerebral arteries.
  10. (2007). Acute hypoxia induces vasodilation and increases coronary blood flow by activating inward rectifier K(+) channels.
  11. (1986). Allosteric effects of Mg2+ on the gating of Ca2+-activated K+ channels from mammalian skeletal muscle.
  12. and dioctanoylglycerol stimulate membrane association of protein kinase C and have a negative inotropic effect mediated by changes in cytosolic Ca2+ in adult rat cardiac myocytes.
  13. (2001). Angiotensin II inhibits and alters kinetics of voltage-gated K+ channels of rat arterial smooth muscle.
  14. (2001). Angiotensin II inhibits rat arterial KATP channels by inhibiting steady-state protein kinase A activity and activating protein kinase Ce.
  15. (1996). Autonomic neuromuscular transmission at a varicosity.
  16. (1991). Bell-shaped calcium-response curves of ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum.
  17. (2004). Beta1-subunit of MaxiK channel in smooth muscle: A key molecule which tunes muscle mechanical activity.
  18. (1990). Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci.
  19. (1991). Block of calcium-activated potassium channels in mammalian arterial myocytes by tetraethylammonium ions.
  20. (1998). Ca2+ channels, ryanodine receptors and Ca2+-activated K+ channels: A functional unit for regulating arterial tone.
  21. (2002). Ca2+ regulation in guinea-pig colonic smooth muscle: The role of the na+-Ca2+ exchanger and the sarcoplasmic reticulum.
  22. (1994). Caffeine activates a ca(2+)-permeable, nonselective cation channel in smooth muscle cells.
  23. (1992). Caffeine-induced release and reuptake of Ca2+ by Ca2+ stores in myocytes from guinea-pig urinary bladder.
  24. (1991). Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release.
  25. (1990). Calcium channels, potassium channels, and voltage dependence of arterial smooth muscle tone.
  26. (1990). Calcium release mechanisms in smooth muscle.
  27. (1992). Calcium-dependent immediate feedback control of inositol 1,4,5-triphosphate-induced Ca2+ release.
  28. (1994). Calmodulin and the regulation of smooth muscle contraction.
  29. (2000). cAMP-dependent vasodilators cross-activate the cGMP-dependent protein kinase to stimulate BK ca channel activity in coronary artery smooth muscle cells.
  30. (1996). Characteristics and physiological role of the ca(2+)-activated cl- conductance in smooth muscle.
  31. (1998). Characteristics of single, large-conductance calciumdependent potassium channels (BKCa) from smooth muscle cells isolated from the rabbit mesenteric artery.
  32. (1998). Characterization and function of Ca(2+)-activated K+ channels in arteriolar muscle cells.
  33. (1997). Characterization of action potentialtriggered [Ca2+]i transients in single smooth muscle cells of guinea-pig ileum.
  34. (1995). Characterization of and modulation by a beta-subunit of a human maxi KCa channel cloned from myometrium.
  35. (1987). Characterization of calcium-activated potassium channels in single smooth muscle cells using the patch-clamp technique.
  36. (2007). Charcterisation of largeconductance calcium-activated potassium channels (BK(Ca)) in human NT2-N cells.
  37. (2001). Coupling strength between localized ca(2+) transients and K(+) channels is regulated by protein kinase C.
  38. (2002). Crosstalk between ryanodine receptors and IP(3) receptors as a factor shaping spontaneous ca(2+)-release events in rabbit portal vein myocytes.
  39. (1987). Data transformations for improved display and fitting of single-channel dwell time histograms.
  40. (1996). Depolarization-evoked increases in cytosolic calcium concentration in isolated smooth muscle cells of rat portal vein.
  41. (1996). Determinant for beta-subunit regulation in highconductance voltage-activated and ca(2+)-sensitive K+ channels: An additional transmembrane region at the N terminus.
  42. (2003). Developmental differences in Ca2+-activated K+ channel activity in ovine basilar artery.
  43. (2007). Diabetes downregulates large-conductance Ca2+-activated potassium beta 1 channel subunit in retinal arteriolar smooth muscle. Circ Res.
  44. (1991). Dual action of endothelin-1 on the Ca2+-activated K+ channel in smooth muscle cells of porcine coronary artery.
  45. (1997). Effects of CP-060S on membrane channels in vascular smooth muscle cells from guinea pig.
  46. (1996). Eight potassium channel families revealed by the C. elegans genome project.
  47. (2005). Electrophysiological and molecular identification of voltage-gated sodium channels in murine vascular myocytes.
  48. (2000). Electrophysiological effects of endothelin-1 and their relationship to contraction in rat renal arterial smooth muscle. bjp 130,
  49. (2004). Endocytosis as a mechanism for tyrosine kinasedependent suppression of a voltage-gated potassium channel.
  50. (1998). Endothelin-1 activates phospholipases and channels at similar concentrations in porcine coronary arteries.
  51. (2000). Endothelin-1 and photoreleased diacylglycerol increase L-type Ca2+ current by activation of protein kinase C in rat ventricular myocytes.
  52. (2002). Endothelin-1--induced enhancement of coronary smooth muscle contraction via MAPK-dependent and MAPK-independent [ca(2+)](i) sensitization pathways.
  53. (2007). Endothelin-1-induced signaling pathways in vascular smooth muscle cells.
  54. (1999). Endothelium-derived hyperpolarizing factor but not NO reduces smooth muscle Ca2+ during acetylcholine-induced dilation of microvessels.
  55. (2004). Essential role for smooth muscle BK channels in alcohol-induced cerebrovascular constriction.
  56. (2003). ET-1 activates Ca2+ sparks in PASMC: Local Ca2+ signaling between inositol trisphosphate and ryanodine receptors.
  57. (2002). Evidence for endocytosis of ROMK potassium channel via clathrin-coated vesicles.
  58. (2007). Evidence that a Ca2+ sparks/STOCs coupling mechanism is responsible for the inhibitory effect of caffeine on electromechanical coupling in guinea pig ureteric smooth muscle.
  59. (1981). Exchange characteristics of the noradrenaline-sensitive calcium store in vascular smooth muscle cells or rabbit ear artery.
  60. (1998). Frequency modulation of Ca2+ sparks is involved in regulation of arterial diameter by cyclic nucleotides.
  61. (1999). Functional coupling of ryanodine receptors to KCa channels in smooth muscle cells from rat cerebral arteries.
  62. (1995). Functional role of the beta subunit of high conductance calcium-activated potassium channels.
  63. (2001). Gating and conductance properties of BK channels are modulated by the S9-S10 tail domain of the alpha subunit. A study of mSlo1 and mSlo3 wild-type and chimeric channels.
  64. (2006). Glucose reduces endothelin inhibition of voltage-gated potassium channels in rat arterial smooth muscle cells.
  65. (1990). Highaffinity binding sites for [3H]saxitoxin are associated with voltage-dependent sodium channels in portal vein smooth muscle.
  66. (1999). Human and rodent MaxiK channel betasubunit genes: Cloning and characterization.
  67. (1998). Hydrogen peroxide relaxes porcine coronary arteries by stimulating BKCa channel activity.
  68. (2003). Hypothesis for the initiation of vasomotion.
  69. (2002). Inhibition of proteintyrosine phosphatase stimulates the dynamin-dependent endocytosis of ROMK1.
  70. (2003). Inositol 1,4,5-trisphosphate receptors modulate Ca2+ sparks and Ca2+ store content in vas deferens myocytes.
  71. (1984). Inositol 1,4,5-trisphosphate releases Ca2+ from intracellular store sites in skinned single cells of porcine coronary artery.
  72. (1998). Inositol 1,4,5-trisphosphatem and ryanodinemsensitive Ca2+ release channel-dependent Ca2+ signalling in rat portal vein myocytes.
  73. (2000). Intracellular calcium events activated by ATP in murine colonic myocytes.
  74. (2007). Intracellular cAMP: the "switch that triggers on "spontaneous transient outward currents" generation in freshly isolated myocytes from thoracic aorta.
  75. (2005). Involvement of BKCa alpha subunit tyrosine phosphorylation in vascular hyporesponsiveness of superior mesenteric artery following hemorrhagic shock in rats.
  76. (2001). Ion channels of excitable membranes.
  77. (2005). IP3-mediated Ca2+ increases do not involve the ryanodine receptor, but ryanodine receptor antagonists reduce IP3-mediated Ca2+ increases in guinea-pig colonic smooth muscle cells.
  78. (1990). Isolated guinea pig coronary smooth muscle cells. acetylcholine induces hyperpolarization due to sarcoplasmic reticulum calcium release activating potassium channels.
  79. (1998). K+ channel modulation in arterial smooth muscle.
  80. (1988). Kinetic states and modes of single large-conductance calcium-activated potassium channels in cultured rat skeletal muscle.
  81. (2006). Large-conductance, calciumactivated potassium channels: Structural and functional implications.
  82. (1995). Major difference between rat and guinea-pig ureter in the ability of agonists and caffeine to release Ca2+ and influence force.
  83. (1998). Maxi-K(ca), a unique member of the voltage-gated K channel superfamily.
  84. (2000). Mice with disrupted BK channel beta1 subunit gene feature abnormal Ca2+ spark/STOC coupling and elevated blood pressure.
  85. (2005). Modulation of agonist-induced
  86. (1993). Molecular and biophysical view of the Ca channel: a hypothesis regarding oligomeric structure, channel clustering, and macroscopic current.
  87. (1999). Molecular basis for the inactivation of Ca2+- and voltage-dependent BK channels in adrenal chromaffin cells and rat insulinoma tumor cells.
  88. (1999). Molecular basis of fast inactivation in voltage and Ca2+-activated K+ channels: A transmembrane beta-subunit homolog.
  89. (1992). Multiple effects of ryanodine on intracellular free Ca2+ in smooth muscle cells from bovine and porcine coronary artery: Modulation of sarcoplasmic reticulum function.
  90. (1995). Multiple types of ryanodine receptor/Ca2+ release channels are expressed in vascular smooth muscle.
  91. (2003). Nitric oxide-induced decrease in calcium sensitivity of resistance arteries is attributable to activation of the myosin light chain phosphatase and antagonized by the RhoA/Rho kinase pathway.
  92. (1988). Noradrenaline contracts arteries by activating voltage-dependent calcium channels.
  93. (1902). On the local reactions of the arterial wall to changes of internal pressure.
  94. (1995). Physiological roles and properties of potassium channels in arterial smooth muscle.
  95. (2000). PKA phosphorylation dissociates FKBP12.6 from the calcium release channel (ryanodine receptor) : Defective regulation in failing hearts.
  96. (2004). PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase.
  97. (2005). PKC independent block of K+ channels by 1,2-dioctanyoyl-sn-glycerol (DOG).
  98. (2002). Potassium (BK(Ca)) currents are reduced in microvascular smooth muscle cells from insulin-resistant rats.
  99. (1996). Potassium channels in vascular smooth muscle.
  100. (2008). Preserved BK channel function in vasospastic myocytes from a dog model of subarachnoid hemorrhage.
  101. (2003). Properties of BK(ca) channels formed by bicistronic expression of hSloalpha and beta1-4 subunits in HEK293 cells.
  102. (1989). Properties of calcium stores and transient outward currents in single smooth muscle cells of rabbit intestine.
  103. (1982). Properties of single calcium-activated potassium channels in cultured rat muscle.
  104. (1993). Properties of spontaneous inward currents in rabbit pulmonary artery smooth muscle cells. Pflügers Archiv European
  105. (2005). Protein kinase C isoforms as specific targets for modulation of vascular smooth muscle function in hypertension. biochem pharm
  106. (1999). Protein kinase C reduces the KCa current of rat tail artery smooth muscle cells.
  107. (1995). Protein kinase cindependent inhibition of the Ca2+-activated K+ channel by angiotensin II and endothelin1.
  108. (2006). Reduced Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels from arteries of Type 2 diabetic Zucker diabetic fatty rats.
  109. (1991). Regenerative release of calcium from functionally discrete subcellular stores by inositol trisphosphate.
  110. (2000). Regulation of basal intracellular calcium concentration by the sarcoplasmic reticulum in myocytes from the rat gastric antrum.
  111. (1998). Regulation of cardiac muscle Ca2+ release channel by sarcoplasmic reticulum lumenal Ca2+.
  112. (2001). Regulation of ion channels by protein tyrosine phosphorylation.
  113. (1996). Regulation of ion channels in smooth muscles by calcium.
  114. (1997). Regulation of spontaneous transient outward potassium currents in human coronary arteries.
  115. (1997). Regulation of the cytosolic Ca2+ concentration by Ca2+ stores in single smooth muscle cells from rat cerebral arteries.
  116. (1995). Relaxation of arterial smooth muscle by calcium sparks.
  117. (2001). Role of phospholamban in the modulation of arterial Ca(2+) sparks and Ca(2+)-activated K(+) channels by cAMP.
  118. (1998). Role of protein kinase C in endothelin-1-induced contraction of human myometrium.
  119. (2000). Role of the beta1 subunit in large-conductance Ca(2+)-activated K(+) channel gating energetics. mechanisms of enhanced ca(2+) sensitivity.
  120. (2002). Ryanodine receptor calcium release channels.
  121. (1972). Sarcoplasmic reticulum and excitationcontraction coupling in mammalian smooth muscles.
  122. (1996). Sarcoplasmic reticulum lumenal Ca2+ has access to cytosolic activation and inactivation sites of skeletal muscle Ca2+ release channel.
  123. (1999). Signaling mechanisms underlying the vascular myogenic response.
  124. (1999). Simultaneous binding of two protein kinases to a calcium-dependent potassium channel.
  125. (1999). Single-channel properties of BK-type calciumactivated potassium channels at a cholinergic presynaptic nerve terminal.
  126. (1991). Sodium currents in smooth muscle cells freshly isolated from stomach fundus of the rat and ureter of the guinea-pig.
  127. (1986). Spontaneous transient outward currents in single visceral and vascular smooth muscle cells of the rabbit.
  128. (2002). Spontaneous transient outward ZhuGe
  129. (2002). Stepwise contribution of each subunit to the cooperative activation of BK channels by Ca2+.
  130. Superresolution three-dimensional images of fluorescence in cells with minimal light exposure.
  131. (1999). The beta subunit increases the Ca2+ sensitivity of large conductance Ca2+-activated potassium channels by retaining the gating in the bursting states.
  132. (2005). The latch-bridge hypothesis of smooth muscle contraction.
  133. (2006). The number and spatial distribution of IP3 receptors underlying calcium puffs in xenopus oocytes.
  134. (1986). The presence of Na+ channels in myometrial smooth muscle cells is revealed by specific neurotoxins.
  135. (2004). The sarcoplasmic reticulum and sarcolemma together form a passive Ca2+ trap in colonic smooth muscle.
  136. (2004). The sarcoplasmic reticulum, Ca2+ trapping, and wave mechanisms in smooth muscle.
  137. (2002). The signal transduction of endothelin-1-induced circular smooth muscle cell contraction in cat esophagus.
  138. (1992). Three additional inositol 1,4,5-trisphosphate receptors: Molecular cloning and differential localization in brain and peripheral tissues.
  139. (1994). Transmembrane topology and sites of N-glycosylation of inositol 1,4,5- trisphosphate receptor.
  140. (1994). Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels.
  141. (2005). TRPV4 forms a novel Ca2+ signalling complex with ryanodine receptors and BKCa channels.
  142. (2005). TTX-sensitive voltage-gated na+ channels are expressed in mesenteric artery smooth muscle cells.
  143. (2002). Tyrosine phosphorylation of Kv1.2 modulates its interaction with the actin-binding protein cortactin.
  144. (1998). Variability in spontaneous subcellular calcium release in guinea-pig ileum smooth muscle cells.
  145. (1991). Vascular smooth muscle contraction induced by Na+ channel activators, veratridine and batrachotoxin.
  146. (2000). Vasoregulation by the beta1 subunit of the calcium-activated potassium channel.
  147. (1998). Versatility of the angiotensin II type 1 receptor.
  148. (2000). Voltage and Ca2+ activation of single large-conductance Ca2+-activated K+ channels described by a two-tiered allosteric gating mechanism.
  149. (1998). Voltage dependence of Ca2+ sparks in intact cerebral arteries.
  150. (2001). Voltage dependence of the coupling of Ca2+ sparks to BKCa channels in urinary bladder smooth muscle.
  151. (1997). Voltagecontrolled gating in a large conductance Ca2+-sensitive K+ channel (hslo).

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