Neurotrophic control of colchicine effects on muscle?

Abstract

COLCHICINE, a substance known to block axonal transport1,2, has been reported to mimic the effects of denervation on mammalian skeletal muscles3–5. These effects, which include an increased extrajunctional sensitivity to acetylcholine (Ach) and a fall in resting membrane potential, occur a few days after colchicine is applied locally to the nerve in doses that do not seem to interfere with nerve impulse conduction, neuromuscular transmission, or muscle tension evoked by stimulation of the nerve3–5. It seems, therefore, that denervation-like changes may be induced in the presence of normal muscle activity and this suggestion is supported by experiments reported here in which the diaphragms of rats with apparently normal respiration became supersensitive to Ach after injection of colchicine into one of the legs (mean extrajunctional Ach sensitivity of 22 fibres from three rats was 4.6 mV nC−1 range 0–30 mV nC−1). It has been suggested that colchicine produces these changes in muscle by blocking some component of axonal transport, thus interfering with the neurotrophic control of muscle3,4. Colchicine also has a systemic effect5, however, and its effect on muscle might be direct and occur independently of any of its effects on nerve. Here I examine this possibility.