Possible role of Na(+)-Ca2+ exchange in the regulation of contractility in isolated adult ventricular myocytes from rat and guinea pig.
Action potentials and developed contractions of externally unloaded single ventricular myocytes isolated from adult rat and guinea pig hearts were recorded by means of an optical system for recording contractile activity during regular stimulation by microelectrodes. Under control conditions, the shortenings (twitches) in the rat myocytes were fully inhibited by 0.1 microM ryanodine, but they were rather insensitive to the Ca2+ blocker 0.2-0.5 microM nifedipine. In contrast, the contractions of the isolated guinea pig ventricular myocytes were greatly suppressed by 0.2-0.5 microM nifedipine (to less than 30%), while they were only slightly reduced by 1 microM ryanodine. When the Na+ gradient was decreased by reducing [Na]o or by elevating [Na]i in the presence of veratridine, the twitch contractions were increased in both species. The effect of reduced [Na]o on twitch contractions was not affected by ryanodine in either type of myocytes, while nifedipine still fully abolished the twitches in the guinea pig cells, indicating a strong dependence of guinea pig contractions on Ca2+ influx. On the other hand, the effect of a reduced Na gradient by veratridine was more complex; the usual twitch (phasic component) was increased and it was followed by a second (tonic) component which relaxed only after the repolarization of the action potential. While the phasic component was decreased by nifedipine and ryanodine in the usual way (as in the controls), the sustained contractions (lasting up to several seconds) were ryanodine and nifedipine insensitive. Furthermore, the cardiomyocytes of both species exposed to strontium in place of external calcium still exhibited all the effects observed when reducing the Na+ gradient.(ABSTRACT TRUNCATED AT 250 WORDS)
Horackova
M
M
Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, N.S., Canada.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology; D066298:In Vitro Techniques; D007474:Ion Exchange; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D012964:Sodium / Q000502:physiology*; D014701:Veratridine / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014701:Veratridine; D012964:Sodium; D002118:Calcium