Abstract
The steps that couple depolarization of the cardiac cell membrane
to initiation of contraction remain controversial. Depolarization
triggers a rise in intracellular free Ca$^2+$ which activates
contractile myofilaments. Most of this Ca$^2+$ is released from
the sarcoplasmic reticulum (SR). Two fundamentally different mechanisms
have been proposed for SR Ca$^2+$ release: Ca$^2+$-induced
Ca$^2+$ release (CICR) and a voltage-sensitive release mechanism
(VSRM). Both mechanisms operate in the same cell and may contribute
to contraction. CICR couples the release of SR Ca$^2+$ closely
to the magnitude of the L-type Ca$^2+$ current. In contrast,
the VSRM is graded by membrane potential rather than Ca$^2+$
current. The electrophysiological and pharmacological characteristics
of the VSRM are strikingly different from CICR. Furthermore, the
VSRM is strongly modulated by phosphorylation and provides a new
regulatory mechanism for cardiac contraction. The VSRM is depressed
in heart failure and may play an important role in contractile dysfunction.
This review explores the operation and characteristics of the VSRM
and CICR and discusses the impact of the VSRM on our understanding
of cardiac excitation-contraction coupling.
- 1-methyl-3-isobutylxanthine,
- 11299192
- activators,
- amp,
- amrinone,
- animals,
- blockers,
- calcium
- calcium,
- channel
- channels,
- chemical,
- comparative
- contraction,
- cyclic
- electrophysiology,
- enzyme
- forskolin,
- gov't,
- guinea
- heart,
- humans,
- in
- inhibitors,
- male,
- membrane
- myocardial
- myocardium,
- non-u.s.
- phosphodiesterase
- pigs,
- potentials,
- research
- reticulum,
- sarcoplasmic
- stimulation,
- study,
- support,
- vitro,
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