Calcium channels and intracellular calcium release are pharmacologically different in frog skeletal muscle.
The pharmacology of Ca2+ channels and intracellular Ca2+ release from the sarcoplasmic reticulum (s.r.) were compared by injecting Ca2+ channel blockers into the cytoplasm and observing contraction under voltage clamp of frog skeletal muscle fibres, a preparation that contracts only in response to Ca2+ release from the s.r. A method for quantifying intracellular injections by co-injecting a fluorescent dye is described. Nifedipine injected into cells blocks Ca2+ current through the cell membrane showing that nifedipine is active when applied to the cytoplasmic side of the membrane in which Ca2+ channels are located. Neither the presence of Ca2+ channel blockers in the extracellular medium nor 24 h incubation in nifedipine and D-600 affect contraction. Nifedipine and D-600 injected to intracellular concentrations much greater than necessary to block Ca2+ channels do not affect contraction. The presence of 30 microM-D-600 during K+ contractures caused paralysis but 20 microM-nifedipine did not. Thus, contracture-dependent D-600 paralysis is not due to blockade of the transverse tubule Ca2+ channel. It is concluded that: (a) a functioning Ca2+ channel on the cell membrane is not necessary to trigger Ca2+ release from the s.r.; (b) s.r. Ca2+ release and Ca2+ channels are pharmacologically different.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011896:Rana temporaria; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013997:Time Factors
D002121:Calcium Channel Blockers; D007473:Ion Channels; D005711:Gallopamil; D009543:Nifedipine; D011188:Potassium; D002118:Calcium