Modulation of action potential by [Ca2+]i in modeled rat atrial and guinea pig ventricular myocytes.
We simulated mechanisms that increase Ca2+ transients with two models: the Luo-Rudy II model for guinea pig (GP) ventricle (GP model) representing long action potential (AP) myocytes and the rat atrial (RA) model exemplifying myocytes with short APs. The interventions were activation of stretch-gated cationic channels, increase of intracellular Na+ concentration ([Na+]i), simulated bet-adrenoceptor stimulation, and Ca2+ accumulation into the sarcoplasmic reticulum (SR). In the RA model, interventions caused an increase of AP duration. In the GP model, AP duration decreased except in the simulated beta-stimulation where it lengthened APs as in the RA model. We conclude that the changes in the APs are significantly contributed by the increase of the Ca2+ transient itself. The AP duration is controlled differently in cardiac myocytes with short and long AP durations. With short APs, an increase of the Ca2+ transient promotes an inward current via Na+/Ca2+-exchanger lengthening the AP. This effect is similar regardless of the mechanism causing the increase of the Ca2+ transient. With long APs the Ca2+ transient increase decreases the AP duration via inactivation of the L-type Ca2+ current. However, L-type current increase (as with beta-stimulation) increases the AP duration despite the simultaneous Ca2+ transient augmentation. The results explain the dispersion of AP changes in myocytes with short and long APs during interventions increasing the Ca2+ transients.
Han
Chunlei
C
Division of Biophysics, Department of Physical Sciences, and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland.
Tavi
Pasi
P
Weckström
Matti
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000502:physiology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006325:Heart Atria; D006352:Heart Ventricles; D007700:Kinetics; D008955:Models, Cardiovascular; D009206:Myocardium / Q000166:cytology; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D013997:Time Factors
D012964:Sodium; D002118:Calcium