Na + -Ca 2+ Exchange Current and Submembrane [Ca 2+ ] During the Cardiac Action Potential

Abstract

Na + -Ca 2+ exchange (NCX) is crucial in the regulation of [Ca 2+ ] 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 ( I NCX ) varies during a rabbit ventricular action potential (AP). First, we measured the steady-state voltage and [Ca 2+ ] i dependence of I NCX under conditions when [Ca 2+ ] i was heavily buffered. We then used this relationship to infer the submembrane [Ca 2+ ] i ([Ca 2+ ] sm ) sensed by NCX during a normal AP and [Ca 2+ ] i transient (when the AP was interrupted to produce an I NCX tail current). The [Ca 2+ ] i dependence of I NCX at −90 mV allowed us to convert the peak inward I NCX tail currents to [Ca 2+ ] sm . Peak [Ca 2+ ] sm measured via this technique was >3.2 μmol/L within <32 ms of the AP upstroke (versus peak [Ca 2+ ] i of 1.1 μmol/L at 81 ms measured with the global Ca 2+ indicator indo-1). The voltage and [Ca 2+ ] sm dependence of I NCX allowed us to infer I NCX during the normal AP and Ca 2+ transient. The early rise in [Ca 2+ ] sm causes I NCX to be inward for the majority of the AP. Thus, little Ca 2+ influx via NCX is expected under physiological conditions, but this can differ among species and in pathophysiological conditions.