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Effects of ryanodine receptor agonist 4-chloro-m-cresol on myoplasmic free Ca2+ concentration and force of contraction in mouse skeletal muscle
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
1998 (English)In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 24, no 2, 105-115 p.Article in journal (Refereed) Published
Abstract [en]

In single mouse skeletal muscle fibers injected with fluorescent Ca2+ indicator Indo-1, 4-chloro-m-cresol (chlorocresol, 4-CmC) and its lipophilic analogue 4-chloro-3-ethylphenol (4-CEP) increased resting myoplasmic free [Ca2+] ([Ca2+]i) in a dose-dependent manner. In this regard, 4-CEP was more potent than 4-CmC and both were more potent than caffeine. High concentrations of 4-CmC (1 mM) or 4-CEP (500 microM) caused large and irreversible increase in resting [Ca2+]i leading to contracture. 4-CmC potentiated the [Ca2+]i increase and force of contraction induced by tetanic stimulation. Unlike caffeine, 4-CmC did not affect the activity of sarcoplasmic reticulum Ca2+ pump or the myofibrillar Ca2+ sensitivity. A low concentration of 4-CEP (20 microM) had no effect on resting [Ca2+]i on its own, but it enhanced the resting [Ca2+]i increase induced by caffeine and also potentiated the [Ca2+]i increase and contraction induced by tetanic stimulation. However, a relatively high concentration of 4-CEP (200 microM) inhibited tetanic stimulation-induced [Ca2+]i increase and contraction. Dantrolene, a muscle relaxant, inhibited 4-CmC-induced [Ca2+]i increase under resting conditions. However, when 4-CEP was applied in the presence of dantrolene, there was an exaggerated increase in [Ca2+]i. We conclude that 4-CmC and 4-CEP are potent agonists that can increase [Ca2+]i rapidly and reversibly by activating ryanodine receptors in situ in intact skeletal muscle fibers. These compounds, specially 4-CmC, may be useful for mechanistic and functional studies of ryanodine receptors and excitation-contraction coupling in skeletal muscles.

Place, publisher, year, edition, pages
1998. Vol. 24, no 2, 105-115 p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-132290DOI: 10.1016/S0143-4160(98)90078-1PubMedID: 9803311OAI: oai:DiVA.org:uu-132290DiVA: diva2:357448
Available from: 2010-10-18 Created: 2010-10-18 Last updated: 2010-10-26Bibliographically approved

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