Isoproterenol and GTP gamma S inhibit L-type calcium channels of differentiating rat skeletal muscle cells.
In adult skeletal muscle, G-proteins have been shown to modulate the calcium channels both directly and through a cAMP-dependent phosphorylating mechanism. We have investigated the action of G-proteins on the L-type calcium current in cultured rat muscle cells (myoballs) under voltage clamp in whole cell or perforated patch modes. Intracellular photolytic release of 200 microM GTP gamma S inhibited the L-type calcium current. Inclusion of 500 microM uncaged GTP gamma S in the patch pipette in the whole cell configuration reduced the calcium current by a similar amount. Under perforated patch conditions external application of 10 microM of the beta-adrenergic agonist isoproterenol also reduced the calcium current. Pretreatment of the cells with pertussis toxin reversed the effect of GTP gamma S and removed that of isoproterenol. We conclude that rat myoballs contain beta-adrenergic receptors that inhibit the L-type calcium current, and that this inhibition is mediated by a pertussis toxin-sensitive G-protein.
ARFC, Institute of Animal Physiology and Genetics Research, Babraham, Cambridge, UK.
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Somasundaram
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Tregear
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000528:radiation effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002454:Cell Differentiation; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology* / Q000031:analogs & derivatives; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology / Q000528:radiation effects; D015640:Ion Channel Gating / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology*; D009132:Muscles / Q000166:cytology / Q000187:drug effects*; D037342:Pertussis Toxin; D010782:Photolysis; D051381:Rats; D017208:Rats, Wistar / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013873:Thionucleotides / Q000494:pharmacology / Q000528:radiation effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
C057003:1-(2-nitro)phenylethyl-P(3)-guanosine 5'-O-(3-thio)triphosphate; D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C029273:P(3)-1-(2-nitro)phenylethyladenosine 5'-triphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D002118:Calcium