Sodium-calcium exchange in mammalian heart: current-voltage relation and intracellular calcium concentration.
Membrane currents and changes in intracellular calcium ion concentration ([Ca2+]i) have been recorded that can be attributed to the operation of an electrogenic, voltage-dependent sodium-calcium (Na-Ca) exchanger in mammalian heart cells. Single guinea-pig ventricular myocytes under voltage clamp were perfused internally with the fluorescent Ca2+-indicator, fura-2, and changes in [Ca2+]i and membrane current that resulted from Na-Ca exchange were isolated through the use of various organic channel blockers (verapamil, TTX), impermeant ions (Cs+, Ni2+), and inhibitors of sarcoplasmic reticulum (ryanodine). The I-V relation of Na-Ca exchange was obtained from the Ni2+-sensitive current elicited by ramp repolarization from +90 mV to -80 mV. Ramps were sufficiently rapid that little change in [Ca2+]i occurred during the ramp. The (constant) [Ca2+]i during the ramp was varied over the range 100 nM to 1000 nM by varying the amplitude and duration of a pre-pulse to the ramp. The reversal potential of the Ni2+-sensitive ramp current varied linearly with 1n[( Ca2+])i. The I-V relations at different [Ca2+]i over the range -60 mV to +140 mV were in reasonable accord with the predictions of a simple, simultaneous scheme of Na-Ca exchange, on the basis that only [Ca2+]i had changed. The relationship between [Ca2+]i and current at a constant membrane voltage was also in accord with this scheme. We suggest that Ca2+-fluxes through the exchanger during the cardiac action potential can be understood quantitatively by considering the binding of Ca2+ to the exchanger during the [Ca2+]i-transient and the effects of membrane voltage on the exchanger.
Wier
W G
WG
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Beuckelmann
D J
DJ
D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002352:Carrier Proteins / Q000378:metabolism*; D002586:Cesium / Q000494:pharmacology; D004594:Electrophysiology; D005456:Fluorescent Dyes / Q000032:analysis; D016257:Fura-2; D006168:Guinea Pigs; D007474:Ion Exchange; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D010477:Perfusion; D012433:Ryanodine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger; D013779:Tetrodotoxin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D001572:Benzofurans; D015220:Calcium Channels; D002352:Carrier Proteins; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D012433:Ryanodine; D002586:Cesium; D013779:Tetrodotoxin; D009532:Nickel; D012964:Sodium; D014700:Verapamil; D002118:Calcium; D016257:Fura-2