Altered Elementary Calcium Release Events and Enhanced Calcium Release by Thymol in Rat Skeletal Muscle

P. Szentesi, Henrietta Szappanos, C. Szegedi, M. Gönczi, I. Jóna, Julianna Cseri, László Kovács, L. Csernoch

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Abstract

The effects of thymol on steps of excitation-contraction coupling were studied on fast-twitch muscles of rodents. Thymol was found to increase the depolarization-induced release of calcium from the sarcoplasmic reticulum, which could not be attributed to a decreased calcium-dependent inactivation of calcium release channels/ryanodine receptors or altered intramembrane charge movement, but rather to a more efficient coupling of depolarization to channel opening. Thymol increased ryanodine binding to heavy sarcoplasmic reticulum vesicles, with a half-activating concentration of 144 μM and a Hill coefficient of 1.89, and the open probability of the isolated and reconstituted ryanodine receptors, from 0.09 ± 0.03 to 0.22 ± 0.04 at 30 μM. At higher concentrations the drug induced long-lasting open events on a full conducting state. Elementary calcium release events imaged using laser scanning confocal microscopy in the line-scan mode were reduced in size, 0.92 ± 0.01 vs. 0.70 ± 0.01, but increased in duration, 56 ± 1 vs. 79 ± 1 ms, by 30 μM thymol, with an increase in the relative proportion of lone embers. Higher concentrations favored long events, resembling embers in control, with duration often exceeding 500 ms. These findings provide direct experimental evidence that the opening of a single release channel will generate an ember, rather than a spark, in mammalian skeletal muscle.

Original languageEnglish
Pages (from-to)1436-1453
Number of pages18
JournalBiophysical Journal
Volume86
Issue number3
Publication statusPublished - Mar 2004

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Thymol
Skeletal Muscle
Calcium
Ryanodine Receptor Calcium Release Channel
Sarcoplasmic Reticulum
Excitation Contraction Coupling
Ryanodine
Confocal Microscopy
Rodentia
Muscles
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biophysics

Cite this

Altered Elementary Calcium Release Events and Enhanced Calcium Release by Thymol in Rat Skeletal Muscle. / Szentesi, P.; Szappanos, Henrietta; Szegedi, C.; Gönczi, M.; Jóna, I.; Cseri, Julianna; Kovács, László; Csernoch, L.

In: Biophysical Journal, Vol. 86, No. 3, 03.2004, p. 1436-1453.

Research output: Contribution to journalArticle

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