Voltage-dependent inactivation of L-type Ca2+ currents in guinea-pig ventricular myocytes.
The objective of this study was to describe the kinetics of voltage-dependent inactivation of native cardiac L-type Ca(2+) currents. Whole-cell currents were recorded from guinea-pig isolated ventricular myocytes. Voltage-dependent inactivation was separated from Ca(2+)-dependent inactivation by replacing extracellular Ca(2+) with Mg(2+) and recording outward currents through Ca(2+) channels. Voltage-dependent inactivation accelerated from slow monophasic decay at -30 mV to maximal rapid biphasic decay at +20 mV. Maximal voltage-dependent inactivation occurred with tau(f) approximately equal 30 ms and tau(s) approximately equal 300 ms, the fast component of decay accounted for 70 % of the current amplitude. In basal conditions Ca(2+) current availability was sigmoid. Isoproterenol (isoprenaline) evoked a large increase in a time-independent component of the Ca(2+) current which also increased with depolarisation. This was responsible for the apparent recovery of Ca(2+) channel current availability at positive membrane potentials and thus a U-shaped availability-voltage (A-V) relationship. It is concluded that beta-adrenergic stimulation altered the reaction of native cardiac L-type Ca(2+) channels to membrane voltage. In basal conditions, voltage accelerated inactivation. In isoproterenol, voltage could also reduce inactivation.
Findlay
Ian
I
CNRS UMR 6542, Faculté des Sciences, Université de Tours, Parc de Grandmont, France.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology*; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016276:Ventricular Function
D000318:Adrenergic beta-Agonists; D020746:Calcium Channels, L-Type; D008274:Magnesium; D007545:Isoproterenol; D002118:Calcium