Аннотация
Excitation-contraction coupling in cardiac myocytes occurs by Ca2+-induced
Ca2+ release, where L-type Ca2+ current evokes a larger sarcoplasmic
reticulum (SR) Ca2+ release. The Ca2+-induced Ca2+ release amplification
factor or gain (SR Ca2+ release/I(Ca)) is usually assessed by the
V(m) dependence of current and Ca2+ transients. Gain rises at negative
V(m), as does single channel I(Ca) (i(Ca)), which has led to the
suggestion that the increases of i(Ca) amplitude enhances gain at
more negative V(m). However, I(Ca) = NP(o) x i(Ca) (where NP(o) is
the number of open channels), and NP(o) and i(Ca) both depend on
V(m). To assess how i(Ca) and NP(o) separately influence Ca2+-induced
Ca2+ release, we measured I(Ca) and junctional SR Ca2+ release in
voltage-clamped rat ventricular myocytes using "Ca2+ spikes" (confocal
microscopy). To vary i(Ca) alone, we changed Ca2+(o) rapidly at
constant test V(m) (0 mV) or abruptly repolarized from +120 mV to
different V(m) (at constant Ca2+(o)). To vary NP(o) alone, we altered
Ca2+ channel availability by varying holding V(m) (at constant test
V(m)). Reducing either i(Ca) or NP(o) alone increased excitation-contraction
coupling gain. Thus, increasing i(Ca) does not increase gain at progressively
negative test V(m). Such enhanced gain depends on lower NP(o) and
reduced redundant Ca2+ channel openings (per junction) and a consequently
smaller denominator in the gain equation. Furthermore, modest i(Ca)
(at V(m) = 0 mV) may still effectively trigger SR Ca2+ release, whereas
at positive V(m) (and smaller i(Ca)), high and well-synchronized
channel openings are required for efficient excitation-contraction
coupling. At very positive V(m), reduced i(Ca) must explain reduced
SR Ca2+ release.
- action
- animals;
- caffeine,
- calcium
- calcium,
- cardiac,
- channel
- channel,
- channels,
- confocal;
- contraction;
- drug
- effects/metabolism
- effects/metabolism;
- effects;
- electric
- gating,
- ion
- kinetics;
- l-type,
- membrane
- metabolism;
- microscopy,
- myocardial
- myocytes,
- patch-clamp
- pharmacology;
- potentials;
- rats;
- receptor
- release
- reticulum,
- ryanodine
- sarcoplasmic
- signaling,
- stimulation;
- techniques;
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