Effects of potassium channel-blocking agents on neurons in the inferior mesenteric ganglion in guinea-pig

Abstract

Intracellular recordings were made from neurons ( n = 121) in the inferior mesenteric ganglion (IMG) in guinea-pig. The pharmacological actions of 4-aminopyridine (4-AP), barium ions (Ba 2+) and tetraethylammonium ions (TEA) were studied on IMG cells which received an excitatory, cholinergic input from mechanosensory nerves in the gastrointestinal tract. 4-AP mediated an excitatory action which involved two separate effects. Firstly, 4-AP increased the incidence of spontaneously occurring, fast EPSPs which gave rise to a spontaneous discharge of action potentials. This indirect, excitatory effect was attributed to an increase in the spontaneous release of acetylcholine from excitatory nerves to the IMG. Secondly, 4-AP altered the excitability of IMG cells and brought about burst discharges and continuous discharges of action potentials. This direct, excitatory effect was not dependent on the spontaneous release of acetylcholine; instead, it was attributed to the blockade of a potassium current similar to the A-current ( I A). The excitatory action of Ba 2+ also involved two separate effects. Firstly, Ba 2+ increased the incidence of spontaneously occurring, fast EPSPs which gave rise to a spontaneous discharge of action potentials. This indirect, excitatory effect was interpreted as Ba 2+ mimicking the actions of Ca 2+ to facilitate the spontaneous release of acetylcholine. Secondly, Ba 2+ altered the excitability of IMG cells and brought about a continuous discharge of action potentials. This excitatory effect was attributed to the blockade of a potassium current similar to the M-current ( I M). TEA exerted an excitatory, then inhibitory, action on IMG cells. Initially, TEA brought about the continuous discharge of action potentials; firing gradually arrested as IMG cells depolarized slowly and a depolarizing block of excitation (i.e. inhibition) developed. The block on excitation was relieved by first restoring the resting membrane potential of IMG cells with hyperpolarizing current-clamp. Thereafter, action potentials were elicited by anode-break excitation by temporarily removing the hyperpolarizing current-clamp. The durations of action potentials and afterspike hyperpolarizations were prolonged in the presence of TEA. The effect of TEA on the action potential of IMG cells was attributed to the blockade of the delayed rectifier ( I K). The effect on the afterspike hyperpolarization was considered the indirect consequence of a blockade of I K; it allowed the development of an inward calcium current which enhanced the calcium-activated, potassium current ( I K Ca ) mediating afterhyperpolarizations.