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Differential effects of caffeine and perchlorate on excitation—contraction coupling in mammalian skeletal muscle
Author(s) -
Csernoch László,
Szentesi Péter,
Kovács László
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.00217.x
Subject(s) - biophysics , ryanodine receptor , chemistry , caffeine , depolarization , calcium , membrane potential , skeletal muscle , muscle contraction , endoplasmic reticulum , voltage clamp , permeability (electromagnetism) , membrane , analytical chemistry (journal) , endocrinology , biochemistry , biology , chromatography , organic chemistry
1 Enzymatically dissociated single muscle fibres of the rat were studied under voltage clamp conditions in a double Vaseline gap experimental chamber. Intramembrane charge movement and changes in intracellular calcium concentration ([Ca 2+ ] i ) were measured and the rate of calcium release ( R rel ) from the sarcoplasmic reticulum (SR) was calculated. This enabled the determination of SR permeability and thus the estimation of the transfer function between intramembrane charge movement and SR permeability. 2 Perchlorate (3 m m ) shifted the membrane potential dependence of intramembrane charge movement to more negative voltages without any effect on the steepness or on the maximal available charge. The drug increased SR permeability at every membrane potential but did not alter the peak‐to‐steady level ratio. It also increased the slope of the transfer function, indicating a more efficient coupling between the voltage sensors and the ryanodine receptors. 3 Caffeine (1 m m ), on the other hand, increased SR permeability without altering the voltage dependence of intramembrane charge movement. It neither prolonged the depolarization‐induced increase in [Ca 2+ ] i at short pulse durations nor altered the time to peak of R rel . The augmentation of SR permeability by the drug was more pronounced during the peak caffeine response than during its steady level. This was manifested in a leftward shift of the transfer function rather than an increase in its slope. 4 These observations indicate that perchlorate and caffeine alter the coupling between the voltage sensors and SR calcium release channels in mammalian skeletal muscle. They do not, however, share a common mechanism for enhancing the depolarization‐induced release of calcium from the SR.