Abstract
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.