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(Circulation Research. 2002;90:182.)
© 2002 American Heart Association, Inc.

Cellular Biology

Na⁺-Ca²⁺ Exchange Current and Submembrane [Ca²⁺] During the Cardiac Action Potential

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

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.

Correspondence to Donald M. Bers, PhD, Department of Physiology, Loyola University Chicago, 2160 S First Ave, Maywood, IL 60153.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 (I_NCX) varies during a rabbit ventricular action potential (AP). First, we measured the steady-state voltage and [Ca²⁺]_i dependence of I_NCX 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 I_NCX tail current). The [Ca²⁺]_i dependence of I_NCX at -90 mV allowed us to convert the peak inward I_NCX 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 I_NCX allowed us to infer I_NCX during the normal AP and Ca²⁺ transient. The early rise in [Ca²⁺]_sm causes I_NCX 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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