Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

Mutations in potassium and calcium channel genes have been associated with cardiac arrhythmias. Here, Jensen et al. show that an anion transporter chloride-bicarbonate exchanger AE3 is also responsible for the genetically-induced mechanism of cardiac arrhythmia, suggesting new therapeutic targets for this diseas

MUSCARINIC REGULATION OF THE L-TYPE CALCIUM CURRENT IN ISOLATED CARDIAC MYOCYTES

International audienceMuscarinic agonists regulate the L-type calcium current in isolated cardiac myocytes. The second messengers pathways involved in this regulation are discussed briefly, with particular emphasis on the involvement of cAMP and cGMP pathways

Pharmacological characterization of the receptors involved in the β-adrenoceptor-mediated stimulation of the L-type Ca(2+) current in frog ventricular myocytes

1. The whole-cell patch-clamp was used for studying the effects of various β(1)- and β(2)-adrenoceptor agonists and antagonists on the L-type Ca current (I(Ca)) in frog ventricular myocytes. 2. Dose-response curves for the effects of isoprenaline (non selective β-agonist), salbutamol (β(2)-agonist), dobutamine (β(1)-agonist) on I(Ca) were obtained in the absence and presence of various concentrations of ICI 118551 (β(2)-antagonist), metoprolol (β(1)-antagonist) and xamoterol (partial β(1)-agonist) to derive EC(50) (i.e. the concentration of β-agonist at which the response was 50% of the maximum) and E(max) (the maximal response) values by use of a Michaelis equation. Schild regression analysis was performed to examine whether the antagonists were competitive and to determine the equilibrium dissociation constant (K(B)) for the antagonist-receptor complex. 3. Isoprenaline increased I(Ca) with an EC(50) of 20.0 nM and an E(max) of 597%. ICI 118551 and metoprolol competitively antagonized the effect of isoprenaline with a K(B) of 3.80 nM and 207 nM, respectively. 4. Salbutamol increased I(Ca) with an EC(50) of 290 nM and an E(max) of 512%. ICI 118551 and metoprolol competitively antagonized the effect of salbutamol with a K(B) of 1.77 nM and 456 nM, respectively. 5. Dobutamine increased I(Ca) with an EC(50) of 2.40 μM and an E(max) of 265%. ICI 118551 and metoprolol competitively antagonized the effect of dobutamine with a K(B) of 2.84 nM and 609 nM, respectively. 6. Xamoterol had no stimulating effect on I(Ca). However, xamoterol competitively antagonized the stimulating effects of isoprenaline, salbutamol and dobutamine on I(Ca) with a K(B) of 58–64 nM. 7. We conclude that a single population of receptors is involved in the β-adrenoceptor-mediated regulation of I(Ca) in frog ventricular myocytes. The pharmacological pattern of the response of I(Ca) to the different β-adrenoceptor agonists and antagonists tested suggests that these receptors are of the β(2)-subtype