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.
- 11834700
- action
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- calcium,
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- channels,
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- disease
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- electric
- electrophysiology,
- esophageal
- exchanger,
- failure,
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- fluid,
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- guinea
- heart
- heart,
- humans,
- in
- intracellular
- ion
- kinetics,
- ls,
- male,
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- membrane
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- models,
- muscle
- myocardial
- myocardium,
- neoplasms,
- nickel,
- non-u.s.
- outcome,
- p.h.s.,
- patch-clamp
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