Na+-Ca2+ exchange current and submembrane [Ca2+] during the cardiac action potential

Christopher R. Weber, Valentino Piacentino, Kenneth S Ginsburg, Steven R. Houser, Donald M Bers

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)182-189
Number of pages8
JournalCirculation Research
Issue number2
StatePublished - Feb 8 2002
Externally publishedYes


  • Action potential
  • Calcium
  • Na-Ca exchanger
  • Rabbit

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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