Na-Ca Exchange Current and Submembrane [Ca] During the Cardiac Action Potential

Na-Ca exchange (NCX) is crucial in the regulation of [Ca]i and cardiac contractility, but key details of its dynamic function during the heartbeat are not known. In the present study, we assess how NCX current (INCX) varies during a rabbit ventricular action potential (AP). First, we measured the steady-state voltage and [Ca]i dependence of INCX under conditions when [Ca ]i was heavily buffered. We then used this relationship to infer the submembrane [Ca]i ([Ca ]sm) sensed by NCX during a normal AP and [Ca ]i transient (when the AP was interrupted to produce an INCX tail current). The [Ca ]i dependence of INCX at 290 mV allowed us to convert the peak inward INCX tail currents to [Ca]sm. Peak [Ca ]sm measured via this technique was .3.2 mmol/L within ,32 ms of the AP upstroke (versus peak [Ca]i of 1.1 mmol/L at 81 ms measured with the global Ca 21 indicator indo-1). The voltage and [Ca]sm dependence of INCX allowed us to infer INCX during the normal AP and Ca 21 transient. The early rise in [Ca]sm causes INCX to be inward for the majority of the AP. Thus, little Ca influx via NCX is expected under physiological conditions, but this can differ among species and in pathophysiological conditions. (Circ Res. 2002;90:●●●-●●●.)