Voltage- and cation-dependent inactivation of L-type Ca2+ channel currents in guinea-pig ventricular myocytes.
L-type Ca2+ channel currents in native ventricular myocytes inactivate according to voltage- and Ca2+-dependent processes. This study sought to examine the effect of beta-adrenergic stimulation on the contributions of voltage and Ca2+ to Ca2+ current decay. Ventricular myocytes were enzymatically isolated from guinea-pig hearts. Inward whole-cell Cd2+-sensitive L-type Ca2+ channel currents were recorded with the patch clamp technique and comparison was made between inward currents carried by Ca2+ and either Ba2+, Sr2+ or Na+. In control conditions the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at negative voltages while at positive voltages there was no difference. The relationship between voltage and inactivation for Ca2+ currents was bell-shaped, while that for Ba2+, Sr2+, and Na+ currents was sigmoid. Thus depolarisation progressively replaced Ca2+-dependent inactivation in the fast phase of decay of Ca2+ channel currents with rapid voltage-dependent inactivation. In the presence of isoproterenol (isoprenaline) the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at all measured voltages (-40 to +30 mV). The relationship between voltage and inactivation for Ca2+, Ba2+ and Sr2+ currents was bell-shaped, while that for Na+ currents was sigmoid with less inactivation than under control conditions. Therefore the fast phase of decay of Ca2+ channel currents was now almost entirely due to Ca2+. It is concluded that the relative contributions of Ca2+- and voltage-dependent mechanisms of inactivation of L-type Ca2+ channels in native cardiac myocytes are modulated by beta-adrenergic stimulation influencing the amount of rapid voltage-dependent inactivation.
Findlay
Ian
I
CNRS UMR 6542, Faculté des Sciences, Université de Tours, France. findlay@univ-tours.fr
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002412:Cations / Q000494:pharmacology; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D013324:Strontium / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002412:Cations; D002104:Cadmium; D001464:Barium; D007545:Isoproterenol; D013324:Strontium