Local regulation of the threshold for calcium sparks in rat ventricular myocytes: role of sodium‐calcium exchange

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Abstract
1 To determine whether Na+‐Ca2+ exchange modulates Ca2+ sparks, we studied enzymatically isolated patch clamped rat ventricular myocytes loaded with the Ca2+‐sensitive indicator fluo‐3, using confocal microscopy at 20–22 °C. Two‐dimensional images of Ca2+ sparks were recorded at 240 Hz using a laser scanning confocal microscope, allowing observation of a large area of the cell (820 μm2) at one time. 2 At a holding potential of −75 mV, spontaneous sparks were infrequent. Removal of extracellular Na+ for 520 ms, which in the absence of pipette Na+ should block Na+‐Ca2+ exchange bidirectionally, was associated with a fourfold increase in spark frequency, without a significant change in cytoplasmic [Ca2+], sarcoplasmic reticulum (SR) Ca2+ content, or spark intensity, size or time course. 3 These findings are consistent with a model of excitation‐contraction coupling in which Na+‐Ca2+ exchange locally regulates the resting Ca2+ concentration in the diadic cleft (T‐tubule‐SR junction), thereby modulating the threshold for triggering Ca2+ sparks.