Na(+)-Ca(2+) exchange current and submembrane [Ca(2+)] during the cardiac action potential

Circ Res. 2002 Feb 8;90(2):182-9. doi: 10.1161/hh0202.103940.

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 micromol/L within < 32 ms of the AP upstroke (versus peak [Ca(2+)](i) of 1.1 micromol/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Calcium / metabolism*
  • Cell Membrane / metabolism*
  • Cell Separation
  • In Vitro Techniques
  • Ion Transport / physiology
  • Myocardial Contraction / physiology
  • Myocardium / metabolism*
  • Patch-Clamp Techniques
  • Rabbits
  • Sodium-Calcium Exchanger / metabolism*

Substances

  • Sodium-Calcium Exchanger
  • Calcium