The mechanism of the facilitatory action of edrophonium in cat skeletal muscle

Abstract

1. The effects of edrophonium have been observed in the transversely cut tenuissimus muscle of the cat.2. Concentrations of edrophonium 10(-7)M to 10(-5)M increased the amplitude of the end-plate potential (e.p.p.) but produced no greater increase in time course than previously observed in curarized muscle.3. When the e.p.p. and gross nerve action potential were recorded simultaneously, antidromic discharges were observed in the motor nerve concomitantly with repetitive e.p.ps in the presence of edrophonium.4. Edrophonium produced no effect on the input resistance or equilibrium potential of the end-plate.5. The fractional release of transmitter was significantly increased by edrophonium but there was no increase in the quantal release of transmitter in the transversely cut muscle preparation.6. In curarized muscle edrophonium also increased the quantal release, the size of the available store of transmitter and the rate of refilling of the available store.7. It is concluded that edrophonium facilitates transmission to skeletal muscle by inducing a repetitive antidromic discharge in the nerve, following orthodromic stimulation. The antidromic discharge propagates by axon reflex to other nerve terminals of the same motor unit producing repetitive e.p.ps. It is also suggested that edrophonium antagonizes tubocurarine by acting as a partial agonist at the motor nerve terminal.