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(Circulation Research. 2002;90:118.)
© 2002 American Heart Association, Inc.

Editorials

Na⁺-Ca²⁺ Exchange

Three New Tools

Kenneth D. Philipson

From the Departments of Physiology and Medicine and the Cardiovascular Research Laboratories, UCLA School of Medicine, Los Angeles, Calif.

Correspondence to Dr Kenneth D. Philipson, Cardiovascular Research Laboratories, MRL 3-645, UCLA School of Medicine, Los Angeles, CA 90095-1760. E-mail kphilipson@mednet.ucla.edu

Key Words: Na⁺-Ca²⁺ exchange • action potential • transgenic mice

The contraction of cardiac muscle is initiated by the influx of Ca²⁺ through voltage-sensitive Ca²⁺ channels. Some of the Ca²⁺ entering the cell binds to Ca²⁺ release channels (ryanodine receptors) on the sarcoplasmic reticulum (SR) and triggers a release of Ca²⁺ from the SR. After the subsequent contraction, Ca²⁺ must be removed from the myoplasm to facilitate relaxation. Most Ca²⁺ is pumped back into the SR, but a significant fraction is extruded from the cell by the Na⁺-Ca²⁺ exchanger. In the steady state, the amount of Ca²⁺ leaving the cell via the exchanger equals the amount of Ca²⁺ that enters through Ca²⁺ channels.^1,2

This simple framework explains general aspects of cardiac excitation-contraction coupling but, of course, there are complications and controversy. Some of the controversy revolves around the exact role of the Na⁺-Ca²⁺ exchanger in this scenario. The exchanger can transport Ca²⁺ in either direction across the cell membrane and possibly sometimes mediates Ca²⁺ influx. The direction of net Ca²⁺ transport is determined by three factors: the Na⁺ gradient, the Ca²⁺ gradient, and the membrane potential. During the early phases of the action potential, for example, depolarization favors reversal of the exchanger into the Ca²⁺ influx mode. On the other hand, Ca²⁺ will be rising rapidly at this time as a result of channel openings and SR Ca²⁺ release. An increased intracellular Ca²⁺ level will push the exchanger back into the Ca²⁺ efflux mode.

So, does the Na⁺-Ca²⁺ exchanger contribute significantly to Ca²⁺ influx? Attempts to address . . . [Full Text of this Article]

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