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Modification of excitation‐contraction coupling by 4‐chloro‐ m ‐cresol in voltage‐clamped cut muscle fibres of the frog ( R. pipiens )
Author(s) -
Struk A.,
Melzer W.
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.1469-7793.1999.221ad.x
Subject(s) - depolarization , caffeine , biophysics , chemistry , egta , calcium , analytical chemistry (journal) , endocrinology , chromatography , biology , organic chemistry
1 The effect of 5 μ m 4‐chloro‐ m ‐cresol (4‐CmC) on voltage‐controlled Ca 2+ release was studied in cut muscle fibres of the frog loaded with internal solutions containing 15 mM EGTA. Fibres were voltage clamped using a double Vaseline gap system, and Ca 2+ signals were recorded with the fluorescent indicator dye fura‐2 2 Resting intracellular free Ca 2+ concentration increased from 61 to 100 n m upon application of 4‐CmC. 3 Both peak rate of release of intracellularly stored Ca 2+ and the steady level attained after 50 ms of depolarization increased, but the potentiation of the latter was more pronounced (by a factor of 1.7 versus 1.3). The voltage of half‐maximal activation remained unchanged. 4 Non‐linear intramembranous charge movements showed no significant change in voltage dependence while the maximal charge displaced by depolarization increased by 25%. 5 The dependence of peak release flux on total intramembranous charge was not different in 4‐CmC, but for the steady level of release the steepness of the relation increased by a factor of 1.3. 6 The stimulating effect of 5 μ m 4‐CmC on depolarization‐induced Ca 2+ release resembled the potentiation by 0.5 m m caffeine. However, 0.5 m m caffeine increased the peak and steady levels of the release rate by a similar factor and caused no increase in the resting free calcium concentration, indicating different modes of action of the two substances. 7 Neither 5 μ m 4‐CmC nor 0.5 m m caffeine led to a loss of voltage control of Ca 2+ release during repolarization after short depolarizations, as has been reported previously for caffeine. Potentiated Ca 2+ release could be terminated by repolarization as fast as under control conditions both with 15 m m and 0.1 m m internal EGTA. 8 The effects of 4‐CmC may result from a direct opening of the release channel combined with an enhancement of the transduction mechanism that couples channel opening to displacement of voltage sensor charges.