Circulation Research. 2001
Published online before print December 20, 2001, doi: 10.1161/hh0202.103940
Published online before print December 20, 2001, doi: 10.1161/hh0202.103940
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Submitted on August 20, 2001
Revised on December 6, 2001
Accepted on December 7, 2001
Na+-Ca2+ Exchange Current and Submembrane [Ca2+] During the Cardiac Action Potential
From the Department of Physiology (C.R.W., K.S.G., D.M.B.), Loyola University Chicago, Stritch School of Medicine, Maywood, Ill; Department of Physiology (V.P., S.R.H.), Temple University School of Medicine, Philadelphia, Pa.
* To whom correspondence should be addressed. E-mail: dbers{at}lumc.edu.
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.
Key words: Na+-Ca2+ exchanger • action potential • rabbit • calcium
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