Potentiation of fractional sarcoplasmic reticulum calcium release by totaland free intra-sarcoplasmic reticulum calcium concentration

Our aim was to measure the influence of sarcoplasmic reticulum (SR) calcium content ([Ca](SRT)) and free SR [Ca] ([Ca](SR)) on the fraction of SR calc ium released during voltage clamp steps in isolated rabbit ventricular myoc ytes. [Ca](SRT), as measured by caffeine application, was progressively inc reased by conditioning pulses. Sodium was absent in both the intracellular and in the extracellular solutions to block sodium/calcium exchange. Total cytosolic calcium flux during the transient was inferred from I-Ca, [Ca](SR T), [Ca](i), and cellular buffering characteristics. Fluxes via the calcium current (I-Ca), the SR calcium pump, and passive leak from the SR were eva luated to determine SR calcium release flux (J(rel)), Excitation-contractio n (EC) coupling was characterized with respect to both gain (integral J(rel )/ integral /(Ca) and fractional SR calcium release. Both parameters were v irtually zero for a small, but measurable [Ca](SRT). Gain and fractional SR calcium release increased steeply and nonlinearly with both [Ca](SRT) and [Ca](SR). We conclude that potentiation of EC coupling can be correlated wi th both [Ca](SRT) and [Ca](SR). While fractional SR calcium release was not linearly dependent upon [Ca](SR), intra-SR calcium may play a crucial role in regulating the SR calcium release process.