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(2)f2 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 beta-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 beta-adrenoceptors by isoproterenol, reversed the hibernating kinetic- (but not amplitude-) phenotype toward the awake type. Therefore, an aberrance in the beta-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.
Alekseev
A E
AE
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia. aleka@mayo.edu
Markevich
N I
NI
Korystova
A F
AF
Terzic
A
A
Kokoz
Y M
YM
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000145:classification / Q000187:drug effects / Q000378:metabolism*; D006605:Hibernation / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D012589:Sciuridae
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009543:Nifedipine; D007545:Isoproterenol