Article,

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

, , , , , and .
J. Physiol., (October 1999)

Abstract

1. To determine whether Na$^+$-Ca$^2+$ exchange modulates Ca$^2+$ sparks, we studied enzymatically isolated patch clamped rat ventricular myocytes loaded with the Ca$^2+$-sensitive indicator fluo-3, using confocal microscopy at 20-22 C. Two-dimensional images of Ca$^2+$ sparks were recorded at 240 Hz using a laser scanning confocal microscope, allowing observation of a large area of the cell (820 microm2) 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$^+$-Ca$^2+$ exchange bidirectionally, was associated with a fourfold increase in spark frequency, without a significant change in cytoplasmic Ca$^2+$, sarcoplasmic reticulum (SR) Ca$^2+$ content, or spark intensity, size or time course. 3. These findings are consistent with a model of excitation-contraction coupling in which Na$^+$-Ca$^2+$ exchange locally regulates the resting Ca$^2+$ concentration in the diadic cleft (T-tubule-SR junction), thereby modulating the threshold for triggering Ca$^2+$ sparks.

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