Na+-Ca2+ exchange contributes to increase of cytosolic Ca2+ concentration during depolarization in heart muscle.
The possible role of Na+-Ca2+ exchange in contributing to depolarization-induced increase in cytosolic Ca2+ concentration ([Ca2+]i) of isolated rat ventricular myocytes was investigated. Measured with the Ca2+-sensitive indicator quin 2, [Ca2+]i increased from 177 +/- 12 (mean +/- SE, n = 11) to 468 +/- 41 nM when cells were depolarized with solutions containing 50 mM KCl [high extracellular K+ concentration ([K+]o)]. Approximately 73% of this high-[K+]o-induced increase in [Ca2+]i was abolished by the Ca2+ channel blocker verapamil (5 microM). For cells pretreated with 10 mM caffeine to deplete the Ca2+ stored in sarcoplasmic reticulum, 50 mM KCl still produced an increase in [Ca2+]i, even in the presence of 5 microM verapamil. However, if extracellular Na+ was replaced by Li+ or tris(hydroxymethyl)aminomethane, this increase was completely abolished. The results suggest that, in addition to voltage-sensitive Ca2+ channels, voltage-sensitive Na+-Ca2+ exchange can also contribute to the increase in [Ca2+]i on depolarization. Therefore both Ca2+ transport systems may play important roles in regulating cardiac excitation and contraction.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004987:Ethers / Q000494:pharmacology; D015759:Ionomycin; D008297:Male; D008345:Manganese / Q000494:pharmacology; D008433:Mathematics; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D004987:Ethers; D002110:Caffeine; D008345:Manganese; D015759:Ionomycin; D012964:Sodium; D014700:Verapamil; D011188:Potassium; D002118:Calcium