Abstract
Intracellular Na$^+$ (Na$^+$i) is regulated in cardiac
myocytes by a balance of Na$^+$ influx and efflux mechanisms.
In the normal cell there is a large steady state electrochemical
gradient favoring Na$^+$ influx. This potential energy is used
by numerous transport mechanisms, including Na$^+$ channels and
transporters which couple Na$^+$ influx to either co- or counter-transport
of other ions and solutes. Six sarcolemmal Na$^+$ influx pathways
are discussed in relatively quantitative terms: Na$^+$ channels,
Na$^+$/Ca$^2+$ exchange, Na$^+$/H$^+$ exchange, Na$^+$/Mg2+
exchange, Na$^+$/HCO3- cotransport and Na$^+$/K$^+$/2Cl$^-$
cotransport. Under normal conditions Na$^+$/Ca$^2+$ exchange
and Na$^+$ channels are the dominant Na$^+$ influx pathways,
but other transporters may become increasingly important during altered
conditions (e.g. acidosis or cell volume stress). Mitochondria also
exhibit Na$^+$/Ca$^2+$ antiporter and Na$^+$/H$^+$
exchange activity that are important in mitochondrial function. These
coupled fluxes of Na$^+$ with Ca$^2+$, H$^+$ and HCO3-
make the detailed understanding of Na$^+$i regulation pivotal
to the understanding of both cardiac excitation-contraction coupling
and pH regulation. The Na$^+$/K$^+$-ATPase is the main route
for Na$^+$ extrusion from cells and Na$^+$i is a primary
regulator under physiological conditions. Na$^+$i is higher
in rat than rabbit ventricular myocytes and the reason appears to
be higher Na$^+$ influx in rat with a consequent rise in Na$^+$/K$^+$-ATPase
activity (rather than lower Na$^+$/K$^+$-ATPase function
in rat). This has direct functional consequences. There may also
be subcellular Na$^+$i gradients locally in ventricular myocytes
and this may also have important functional implications. Thus, the
balance of Na$^+$ fluxes in heart cells may be complex, but myocyte
Na$^+$ regulation is functionally important and merits focused
attention as in this issue.
- 12650864
- active,
- adaptation,
- animals,
- antiporter,
- atpase,
- biological
- biological,
- calcium,
- capacitance,
- cardiac,
- cell
- cells,
- comparative
- computer
- cultured,
- diffusion,
- distribution,
- electric
- exchanger,
- gov't,
- h.s.,
- heart
- intracellular
- membrane
- models,
- muscle
- myocytes,
- non-u.s.
- p.,
- p.h.s.,
- physiological,
- potentials,
- rabbits,
- rats,
- research
- sarcolemma,
- simulation,
- size,
- sodium,
- sodium-calcium
- sodium-hydrogen
- space,
- study,
- support,
- tissue
- transport,
- u.s.
- ventricles,
- {n}a$^{+}$-{k}$^{+}$-exchanging
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