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Na$^+$-Ca$^2+$ exchange current and submembrane Ca$^2+$ during the cardiac action potential.

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Circ. Res., 90 (2): 182--189 (февраля 2002)

Аннотация

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.

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