Аннотация
Na$^+$-Ca$^2+$ exchanger and Ca$^2+$ channel are two major
sarcolemmal Ca$^2+$-transporting proteins of cardiac myocytes.
Although the Ca$^2+$ channel is effectively regulated by protein
kinase A-dependent phosphorylation, no enzymatic regulation of the
exchanger protein has been identified as yet. Here we report that
in frog ventricular myocytes, isoproterenol down-regulates the Na$^+$-Ca$^2+$
exchanger, independent of intracellular Ca$^2+$ and membrane
potential, by activation of the beta-receptor/adenylate-cyclase/cAMP-dependent
cascade, resulting in suppression of transmembrane Ca$^2+$ transport
via the exchanger and providing for the well-documented contracture-suppressant
effect of the hormone on frog heart. The beta-blocker propranolol
blocks the isoproterenol effect, whereas forskolin, cAMP, and theophylline
mimic it. In the frog heart where contractile Ca$^2+$ is transported
primarily by the Na$^+$-Ca$^2+$ exchanger, the beta-agonists'
simultaneous enhancement of Ca$^2+$ current, ICa, and suppression
of Na$^+$-Ca$^2+$ exchanger current, INa-Ca would enable
the myocyte to develop force rapidly at the onset of depolarization
(enhancement of ICa) and to decrease Ca$^2+$ influx (suppression
of INa-Ca) later in the action potential. This unique adrenergically
induced shift in the Ca$^2+$ influx pathways may have evolved
in response to paucity of the sarcoplasmic reticulum Ca$^2+$-ATPase/phospholamban
complex and absence of significant intracellular Ca$^2+$ release
pools in the frog heart.
- 8-bromo
- 8643609
- action
- adenosine
- adenylate
- adrenergic
- adrenergic,
- amp,
- animals,
- atpase,
- beta,
- beta-agonists,
- beta-antagonists,
- calcium,
- carrier
- comparative
- contraction,
- cyclase,
- cyclic
- exchanger,
- forskolin,
- gov't,
- heart
- heart,
- in
- isoproterenol,
- kinetics,
- membrane
- monophosphate,
- myocardial
- nickel,
- non-u.s.
- p.h.s.,
- patch-clamp
- pipiens,
- potentials,
- propranolol,
- proteins,
- rana
- receptors,
- research
- reticulum,
- sarcoplasmic
- sodium-calcium
- study,
- support,
- techniques,
- theophylline,
- u.s.
- ventricles,
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