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Evidence for a Sliding Channel Hypothesis for Muscle Excitation‐Contraction Coupling
Author(s) -
Pitake Saumitra,
Ochs Raymond
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.947.23
Subject(s) - ryanodine receptor , biophysics , depolarization , chemistry , voltage dependent calcium channel , cytosol , sarcolemma , calcium , muscle contraction , endoplasmic reticulum , biochemistry , biology , anatomy , membrane , enzyme , organic chemistry
The sarcolemma membrane DHPR of skeletal muscle and the sarcoplasmic reticular (SR) bound ryanodine receptor (RyR), are both Ca 2+ channels that are known to interact in response to sarcolemmal depolarization, transmitting a movement of the DHPR, through physical contact with the RyR, to release of Ca 2+ from the SR lumen to the cytosol through the RyR channel. The mechanism of this excitation‐contraction coupling (ECC) is unknown. We propose the Sliding Channel Hypothesis, in which the DHPR blocks its closely apposed RyR, and moves, under the influence of the electric field imposed by cell depolarization to block a formerly unoccupied RyR, with release of Ca 2+ from the just‐freed RyR. Supporting this hypothesis, we found that ryanodine, the selective inhibitor of the RyR, blocked depolarizationinduced calcium entry through L‐channel (measured by whole‐cell patch clamp). Yet, store‐operated calcium entry (SOCE) was little affected by ryanodine. Furthermore, measurements of cytosolic Ca 2+ by FURA2 fluorescence showed that underconditions of movement of the DHPR – K depolarization or the DHPR agonist BayK – there was an enhanced sensitivity to ryanodine. This suggests a movement of the two channels to enable increased ryanodine binding to the RyR. Under conditions that also increased cytosolic Ca 2+ but did should not induce a relative movement of the channels – added extracellular Ca 2+ or the RyR channel activator methylcresol – there was no change in ryanodine sensitivity. We also propose that the entry of Ca 2+ for the two processes is distinct: directly into the cytosol for ECC, but directly into the SR lumen for CCE.