Abstract
The Na$^+$/Ca$^2+$ exchanger, an ion transport protein, is
expressed in the plasma membrane (PM) of virtually all animal cells.
It extrudes Ca$^2+$ in parallel with the PM ATP-driven Ca$^2+$
pump. As a reversible transporter, it also mediates Ca$^2+$ entry
in parallel with various ion channels. The energy for net Ca$^2+$
transport by the Na$^+$/Ca$^2+$ exchanger and its direction
depend on the Na$^+$, Ca$^2+$, and K$^+$ gradients across
the PM, the membrane potential, and the transport stoichiometry.
In most cells, three Na$^+$ are exchanged for one Ca$^2+$.
In vertebrate photoreceptors, some neurons, and certain other cells,
K$^+$ is transported in the same direction as Ca$^2+$, with
a coupling ratio of four Na$^+$ to one Ca$^2+$ plus one K$^+$.
The exchanger kinetics are affected by nontransported Ca$^2+$,
Na$^+$, protons, ATP, and diverse other modulators. Five genes
that code for the exchangers have been identified in mammals: three
in the Na$^+$/Ca$^2+$ exchanger family (NCX1, NCX2, and NCX3)
and two in the Na$^+$/Ca$^2+$ plus K$^+$ family (NCKX1
and NCKX2). Genes homologous to NCX1 have been identified in frog,
squid, lobster, and Drosophila. In mammals, alternatively spliced
variants of NCX1 have been identified; dominant expression of these
variants is cell type specific, which suggests that the variations
are involved in targeting and/or functional differences. In cardiac
myocytes, and probably other cell types, the exchanger serves a housekeeping
role by maintaining a low intracellular Ca$^2+$ concentration;
its possible role in cardiac excitation-contraction coupling is controversial.
Cellular increases in Na$^+$ concentration lead to increases
in Ca$^2+$ concentration mediated by the Na$^+$/Ca$^2+$
exchanger; this is important in the therapeutic action of cardiotonic
steroids like digitalis. Similarly, alterations of Na$^+$ and
Ca$^2+$ apparently modulate basolateral K$^+$ conductance
in some epithelia, signaling in some special sense organs (e.g.,
photoreceptors and olfactory receptors) and Ca$^2+$-dependent
secretion in neurons and in many secretory cells. The juxtaposition
of PM and sarco(endo)plasmic reticulum membranes may permit the
PM Na$^+$/Ca$^2+$ exchanger to regulate sarco(endo)plasmic
reticulum Ca$^2+$ stores and influence cellular Ca$^2+$ signaling.
- 10390518
- acid
- amino
- animals,
- base
- data,
- exchanger,
- gov't,
- humans,
- kinetics,
- molecular
- p.h.s.,
- relationship,
- research
- sequence
- sequence,
- sodium-calcium
- structure-activity
- support,
- u.s.
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