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Na(+)-Ca(2+) exchange current and submembrane [Ca(2+)] during the cardiac action potential
Christopher R Weber1, Valentino Piacentino, Kenneth S Ginsburg
1Department of Physiology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Circulation Research
|February 9, 2002
Summary
Sodium-calcium exchanger (NCX) dynamics during heartbeats were studied. NCX current is inward for most of the action potential, suggesting limited calcium influx under normal physiological conditions.
Area of Science:
- Cardiovascular Physiology
- Molecular Cardiology
- Ion Transport Mechanisms
Background:
- Sodium-calcium exchanger (NCX) is vital for regulating intracellular calcium ([Ca(2+)](i)) and cardiac contractility.
- The precise dynamic function of NCX throughout the cardiac cycle remains incompletely understood.
Purpose of the Study:
- To investigate the variation of NCX current (I(NCX)) during a rabbit ventricular action potential (AP).
- To determine the submembrane calcium concentration ([Ca(2+)](sm)) sensed by NCX during physiological conditions.
Main Methods:
- Measured steady-state voltage and [Ca(2+)](i) dependence of I(NCX) with heavily buffered intracellular calcium.
- Inferred [Ca(2+)](sm) during AP and [Ca(2+)](i) transients using the characterized I(NCX) dependence.
- Converted peak inward I(NCX) tail currents to [Ca(2+)](sm) at -90 mV.
Main Results:
- Peak [Ca(2+)](sm) exceeded 3.2 micromol/L within 32 ms of the AP upstroke.
- This contrasts with peak global [Ca(2+)](i) of 1.1 micromol/L at 81 ms measured by indo-1.
- Inferred I(NCX) was inward during most of the AP due to the rapid rise in [Ca(2+)](sm).
Conclusions:
- NCX current is predominantly inward during the cardiac action potential under physiological conditions.
- Significant calcium influx via NCX is unlikely in healthy states but may vary across species or in disease.