Sodium-calcium exchange in mammalian heart: current-voltage relation and intracellular calcium concentration |
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Authors: | W G Wier D J Beuckelmann |
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Institution: | (1) Department of Physiology, University of Maryland School of Medicine, 21201 Baltimore, MD, USA |
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Abstract: | 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 occured 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. |
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Keywords: | calcium sodium fura-2 |
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