Na+-Ca2+ exchange (NCX) is crucial in the regulation of [Ca2+]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 [Ca2+]i dependence of INCX under conditions when [Ca2+]i was heavily buffered. We then used this relationship to infer the submembrane [Ca2+]i ([Ca2+]sm) sensed by NCX during a normal AP and [Ca2+]i transient (when the AP was interrupted to produce an INCX tail current). The [Ca2+]i dependence of INCX at -90 mV allowed us to convert the peak inward INCX tail currents to [Ca2+]sm. Peak [Ca2+]sm measured via this technique was >3.2 μmol/L within <32 ms of the AP upstroke (versus peak [Ca2+]i of 1.1 μmol/L at 81 ms measured with the global Ca2+ indicator indo-1). The voltage and [Ca2+]sm dependence of INCX allowed us to infer INCX during the normal AP and Ca2+ transient. The early rise in [Ca2+]sm causes INCX to be inward for the majority of the AP. Thus, little Ca2+ influx via NCX is expected under physiological conditions, but this can differ among species and in pathophysiological conditions.
- Action potential
- Na-Ca exchanger
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine