Comparative analysis of the kinetic characteristics of L-type calcium channels in cardiac cells of hibernators

An undefined property of L-type Ca²⁺ channels is believed to underlie the unique phenotype of hibernating hearts. Therefore. L-type Ca²⁺ channels in single cardiomyocytes isolated from hibernating versus awake ground- squirrels (Citellus undulatus) were compared using the perforated mode of the patch-clamp technique, and interpreted by way of a kinetic model of Ca²⁺ channel behavior based upon the concept of independence of the activation and inactivation processes. We find that, in hibernating ground-squirrels, the cardiac L-type Ca²⁺ current is lower in magnitude when compared to awake animals. Both in the awake or hibernating states, kinetics of L-type Ca²⁺ channels could be described by a d²f₁/²f₂ model with an activation and two inactivation processes. The activation (or d) process relates to the movement of the gating charge. The slow (or f₁) inactivation is associated with movement of gating charge and is current-dependent. The rapid (or f₂) inactivation is a complex process which cannot be represented as a single- step conformational transition induced by the gating charge movement, and is regulated by β-adrenoceptor stimulation. When compared to awake animals, the kinetic properties of Ca²⁺ channels from hibernating ground-squirrels differed in the following parameters: (1) pronounced shift (15-20 mV) toward depolarization in the normalized conductance of both inactivation components, and moderate shift in the activation component; (2) 1.5-2-fold greater time constants; and (3) two-fold greater activation gating charge. Thus, L-type Ca²⁺ channels apparently switch their phenotype during the hibernating transition. Stimulation of β-adrenoceptors by isoproterenol, reversed the hibernating kinetic- (but not amplitude-) phenotype toward the awake type. Therefore, an aberrance in the β-adrenergic system can not fully explain the observed changes in the L-type Ca²⁺ current. This suggests that during hibernation additional mechanisms may reduce the single Ca²⁺ channel- conductance and/or keep a fraction of the cardiac L-type Ca²⁺ channel population in a non active state.