Characterization of end-plate conductance in transected frog muscle: Modification by drugs

J. J. Lambert, N. N. Durant, L. S. Reynolds, R. L. Volle, E. G. Henderson

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Cutaneous pectoris muscles of Rana pipiens were transected distal to the innervated region. Within 10 min, membrane potentials (E(m)'s) of -33 ± 2.5 mV and end-plate potentials (3-15 mV) were recorded unaccompanied by muscle action potentials or twitch. The fall in E(m) was associated with a net loss of [K +](i) and a net gain of [Na +](i). Although input resistance fell by 50% and the space constant was slightly reduced in the transected muscle fibers, end-plates could be adequately voltage-clamped with two microelectrodes. End-plate currents (e.p.c.s.) with rise times of 350 to 700 μsec were recorded as a function of holding potential (V(m)). The current-voltage relationship of peak e.p.c.s. over the range of -70 to +20 mV was linear and the reversal potential (-6.6 ± 2.2 mV) was the same as that found for intact muscle fibers. The decay phase of e.p.c.s could be described as a single exponential at all V(m)'s and had a voltage and temperature dependence similar to that described for e.p.c.s of glycerol-treated muscles. Tubocurarine (0.3 μM) caused a significant decrease in the time constant (τ) of e.p.c. decay and e.p.c. amplitude. The depression of e.p.c. amplitude by tubocurarine was reversed by 4-aminopyridine while the decrease of τ was not. Atropine (10 -4M) caused a monotonic shortening of e.p.c.s at a V(m) of -90 mV but e.p.c.s recorded at +50 mV were biphasic. Lidocaine, a quaternary nitrogen analog of lidocaine (QX314), lobeline and hexafluorenium were studied also in transected muscle and their effects on the parameters of e.p.c. are described. Both lobeline (50 μM) and hexafluorenium caused a decrease of τ and eliminated the voltage dependence of τ at negative V(m)'s. The transected muscle can be used for the study of conductance kinetics of the end-plate and for the study of drug action uncomplicated by the presence of other drugs or Mg ++ to eliminate contraction.

Original languageEnglish
Pages (from-to)62-69
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume216
Issue number1
Early online date1 Jan 1980
Publication statusPublished - 30 Mar 1981

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