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Excitation-contraction coupling in skeletal muscle.
Calcium ions play an important role in intracellular
communication in many cells. In vertebrate twitch muscle fibers, for
example, contraction is normally activated by a depolarization of the
membranes of the transverse tubular system. This leads to a movement
of calcium ions from inside the sarcoplasmic reticulum (SR), where they
are stored, into the myoplasm, where they can bind to the calcium regulatory
sites on troponin so that contraction can occur. My research objectives
are to understand the factors that control the flow of calcium ions
through the calcium channels in the SR membrane (ryanodine receptor
protein). These factors include the voltage across the tubular membranes,
which is sensed by their voltage sensors (the dihydropyrydine receptors),
and free [Ca2+] itself, which can cause calcium-induced calcium release
or calcium inactivation of calcium release. Electrophysiological methods
are used to monitor currents generated by the voltage sensors, and optical
methods are used to monitor the myoplasmic free calcium concentration,
which can be used to estimate SR calcium release.
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Figure caption:
Relative timing of the action potential (AP), myoplasmic free
[Ca] and the rate of Ca release from the sarcoplasmic reticulum
(d[Ca]T/dt) and the binding of Ca to the Ca- regulatory sites
on troponin ([CaTrop]).
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Recent publications:
Hollingworth
S., J. Peet, W.K. Chandler, and S.M. Baylor (2001). Calcium
sparks in intact skeletal muscle fibers of the frog. Journal of
General Physiology. 118: 653-678.
Baylor, S.M., S. Hollingworth, and W.K. Chandler (2002). Comparison
of simulated and measured sparks in intact skeletal muscle fibers of
the frog. Journal of General Physiology. 120: 349-368.
Chandler, W.K., S. Hollingworth, and S.M. Baylor (2003). Simulation of calcium sparks in cut skeletal muscle fibers of the frog. Journal of General Physiology. 121: 311-324.
knox.chandler@yale.edu
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