Na(+)-Ca(2+) exchange current and submembrane [Ca(2+)] during the cardiac action potential.
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.
Weber
Christopher R
CR
Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Piacentino
Valentino
V
Ginsburg
Kenneth S
KS
Houser
Steven R
SR
Bers
Donald M
DM
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002469:Cell Separation; D066298:In Vitro Techniques; D017136:Ion Transport / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D019831:Sodium-Calcium Exchanger; D002118:Calcium