Abstract
In striated muscles, intracellular Ca$^2+$ release is tightly
controlled by the membrane voltage sensor. Ca$^2+$ ions are necessary
mediators of this control in cardiac but not in skeletal muscle,
where their role is ill-understood. An intrinsic gating oscillation
of Ca$^2+$ release-not involving the voltage sensor-is demonstrated
in frog skeletal muscle fibers under voltage clamp. A Markov model
of the Ca$^2+$ release units is shown to reproduce the oscillations,
and it is demonstrated that for Markov processes to have oscillatory
transients, its transition rates must violate thermodynamic reversibility.
Such irreversibility results in permanent cycling of the units through
a ring of states, which requires a source of free energy. Inhibition
of the oscillation by 20 to 40 mM EGTA or partial depletion of Ca$^2+$
in the sarcoplasmic reticulum (SR) identifies the SR Ca$^2+$
gradient as the energy source, and indicates a location of the critical
Ca$^2+$-sensing site at distances greater than 35 nm from the
open channel. These results, which are consistent with a recent demonstration
of irreversibility in gating of cardiac Ca$^2+$ sparks, (Wang,
S.-Q., L.-S. Song, L. Xu, G. Meissner, E. G. Lakatta, E. R�os,
M. D. Stern, and H. Cheng. 2002. Biophys. J. 83:242-251) exemplify
a cell-wide oscillation caused by coupling between ion permeation
and channel gating.
- 12414685
- acid,
- agents,
- algorithms,
- animals,
- biophysics,
- calcium
- calcium,
- chains,
- channel,
- chelating
- dose-response
- drug,
- e
- egtazic
- factors,
- gov't,
- markov
- models,
- muscles,
- oscillometry,
- p.h.s.,
- pipiens,
- rana
- receptor
- relationship,
- release
- research
- reticulum,
- ryanodine
- sarcoplasmic
- statistical,
- support,
- thermodynamics,
- tim,
- u.s.
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