Low efficiency of Ca2+ entry through the Na+-Ca2+ exchanger as trigger for Ca2+ release from the sarcoplasmic reticulum - A comparison between L-type Ca2+ current and reverse-mode Na+-Ca2+ exchange

Sipido, KR;Maes, Marc;Vandewerf, F.
(1997) Circulation Research — Vol. 81, n° 6, p. 1034-1044 (1997)

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  • Sipido, KR
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  • Maes, MarcUCLouvain
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  • Vandewerf, F.
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Abstract
It has been proposed that Ca2+ entry through the Na+-Ca2+ exchanger can contribute significantly to the trigger for Ca2+ release from the sarcoplasmic reticulum (SR). We have compared the characteristics of Ca2+ release triggered by reverse-mode Na+-Ca2+ exchange and by L-type Ca2+ current (I-CaL) during depolarizing steps in single guinea pig ventricular myocytes (whole-cell voltage clamp, flue 3 and fura-red as [Ca2+](i) indicators, 36+/-1 degrees C, K+-based pipette solution with 20 mmol/L [Na+]). Conditioning pulses to +60 mV ensured comparable Ca2+ loading of the SR. In the presence of I-CaL, [Ca2+](i) transients typically have an early and rapid rising phase reflecting Ca2+ release, which has a bell-shaped voltage dependence with a peak at +10 mV. With Ca2+ entry through Na+-Ca2+ exchange only (20 mu mol/L nisoldipine), Ca2+ release flux from the SR is decreased and directly related to the amplitude of the depolarizing step. Ca2+ release is preceded by a significant delay (81+/-21 ms at +20 mV, 24+/-4 ms at +70 mV) related to Ca2+ entry through the exchanger. Triggered release interrupts Ca2+ entry, as evidenced by reversal of the exchanger current. At potentials positive to +40 mV, Ca2+ influx through Na+-Ca2+ exchange, calculated from the outward exchange current, reaches magnitudes comparable to I-CaL, but Ca2+ release due to reverse-mode Na+-Ca2+ exchange still has a significant delay. We calculated trigger efficiency as the ratio between the maximal rate of Ca2+ release and the Ca2+ influx preceding this release; efficiency of reverse-mode Na+-Ca2+ exchange is approximately four times less than that of I-CaL. With both I-CaL and reverse-mode Na+-Ca2+ exchange present, Ca2+ release is triggered by I-CaL, and a contribution of reverse-mode Na+-Ca2+ exchange to the trigger could not be detected at potentials below +60 mV. These characteristics of reverse; mode Na+-Ca2+ exchange predict that its role as a trigger for Ca2+ release during the action potential is likely to be negligible.
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Sipido, K., Maes, M., & Vandewerf, F. (1997). Low efficiency of Ca2+ entry through the Na+-Ca2+ exchanger as trigger for Ca2+ release from the sarcoplasmic reticulum - A comparison between L-type Ca2+ current and reverse-mode Na+-Ca2+ exchange. Circulation Research, 81(6), 1034-1044. https://hdl.handle.net/2078.5/70649 (Original work published 1997)