Effects of 2,3-butanedione monoxime on excitation-contraction coupling in frog twitch fibres.
10 and 30 mM 2,3-butanedione monoxime (BDM) applied extracellularly to voltage-clamped frog skeletal muscle twitch fibres suppressed both Ca2+ release flux and intramembranous charge movement. Both effects could be clearly separated. The early peak of the Ca2+ release flux was suppressed at every test voltage. The steady level attained at the end of a 100 ms clamp depolarization was relatively spared for lower depolarizing pulses, but was as suppressed as the peak at voltages above -20 mV. The intramembranous charge movement was affected mainly in the I gamma component. The drug had a distinct effect on the kinetics of the intramembranous charge movement current around the threshold for Ca2+ release. The three kinetic components of I gamma were simultaneously affected. For more positive depolarizations where the kinetic effect was not evident, the oxime had no significant effect on the charge moved. Under conditions in which I gamma was absent (i.e. stretched fibres, intracellular solutions containing 6 to 10 mM BAPTA), treatment with 10 mM BDM had a small, not significant suppressive effect on the maximum charge moved (Qmax), while it affected Ca2+ release significantly. When 10 mM BDM was applied in the presence of 0.2 mM tetracaine, the local anaesthetic-resistant Ca2+ release flux was not further suppressed by the oxime.
Departamento de Biofísica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
R
R
De Armas
S
S
González
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G
Brum
G
G
Pizarro
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D003931:Diacetyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011892:Rana catesbeiana; D012518:Sarcomeres / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013748:Tetracaine / Q000494:pharmacology
D000779:Anesthetics, Local; D002614:Chelating Agents; D002801:Cholinesterase Reactivators; D013748:Tetracaine; C004717:diacetylmonoxime; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D003931:Diacetyl; D002118:Calcium