NONCHOLINERGIC MECHANISM OF ACTION OF CHOLINERGIC DRUGS ON SQUID AXON MEMBRANES

¹ Department of Physiology and Pharmacology, Duke University Medical Center, Durham, North Carolina

The effects of acetylcholine and other cholinergic drugs on squid axon membranes have been studied by means of internal perfusion and voltage clamp techniques in an attempt to characterize the nature of axonal cholinergic receptors. External application of carbamylcholine, decamethonium and d-tubocurarine at concentrations up to 10 mM had little or no effect on resting and action potentials. Peak transient sodium and steady-state potassium conductances were virtually unaffected by any of these drugs under voltage clamp conditions in agreement with the results on the action potential. When perfused internally at a concentration of 10 mM, acetylcholine, carbamylcholine, hexamethonium and decamethonium had no effect on the resting membrane potential whereas d-tubocurarine hyperpolarized the membrane by 4 mV. The amplitude of the action potential was slightly decreased and its duration prolonged, and peak transient and steady-state conductances were slightly suppressed by internal perfusion of acetylcholine, carbamylcholine and hexamethonium. Decamethonium, at 10 mM, decreased the height of the action potential to 70% of the control and prolonged its duration. It decreased the peak transient conductance to 50% of the control and left steady-state conductance unchanged. d-Tubocurarine, at 10 mM, decreased the height of the action potential to 50% of the control and prolonged its duration remarkably. Both peak transient and steady-state conductances were almost equally suppressed and the effect was concentration-dependent. d-Tubocurarine (10 mM) also slowed the sodium inactivation process. The effects of cholinergic drugs on squid axon membrane are distinctly different from those on postsynaptic membranes. It is concluded that the effects of cholinergic drugs on ionic conductances of axonal membrane of squid giant axon are unrelated to the cholinergic mechanism at postsynaptic membranes.