Profile and kinetics of L-type calcium current during the cardiac ventricular action potential compared in guinea-pigs, rats and rabbits.
The substantial interspecies differences in mammalian cardiac action potentials (APs) are attributed primarily to variations in K+ currents. In a comparative study on isolated ventricular myocytes from guinea-pigs, rabbits and rats, we investigated the influence of the species-based AP differences on the time course of the L-type Ca2+ current (ICa,L). In addition, we tested whether also species-dependent properties of the ICa,L contribute to its time course during the AP. In patch-clamp measurements, ICa,L was characterised using conventional square pulses and digitised APs as command voltages. Special interest was directed to the analysis of the actual time courses of ICa,L, and L-type channel activation and inactivation during APs. Although species-specific differences in AP shape strongly influence the amplitude and the time course of ICa,L, divergence in L-type channel inactivation was found as well. In each species ICa,L inactivation was related to Ca2+ influx via L-type channels. However, while L-type channels showed similar Ca2+ dependency in the rabbit and the rat, a 2-times higher Ca2+ influx was necessary to achieve a given degree of inactivation in the guinea-pig. Thus, inactivation of ICa,L is delayed in the guinea-pig, thereby contributing to the prolonged AP plateau in this species. Comparing the actual time course of ICa,L, and L-type channel activation and inactivation revealed that, in each species, fading of ICa,L during final repolarisation was caused by deactivation (i.e. closure of the channel's d-gate) rather than inactivation.
Linz
K W
KW
Physiological Institute, University of Bonn, Germany. linz@physiol.uni-bonn.de
Meyer
R
R
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002021:Buffers; D002118:Calcium / Q000493:pharmacokinetics; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006531:HEPES / Q000494:pharmacology; D006352:Heart Ventricles / Q000737:chemistry / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D051381:Rats; D011921:Rats, Inbred WKY; D013045:Species Specificity; D019789:Tetraethylammonium / Q000494:pharmacology
D002021:Buffers; D020746:Calcium Channels, L-Type; D002614:Chelating Agents; D004533:Egtazic Acid; D019789:Tetraethylammonium; D006531:HEPES; D002118:Calcium