Enhanced excitability of myenteric AH neurones in the inflamed guinea‐pig distal colon

Abstract

The electrical and synaptic properties of myenteric neurones in normal and inflamed guinea-pig distal colons were evaluated by intracellular microelectrode recording. Chronic inflammation was established 6 days following administration of trinitrobenzene sulfonic acid (TNBS). In S neurones, inflammation only altered synaptic inputs as the amplitude of fast excitatory postsynaptic potentials were significantly larger (31 ± 2 mV compared to 20 ± 1 mV) and they were more likely to receive slow excitatory synaptic input (85% compared to 55%). AH neurones displayed altered electrical properties in colitis compared to control tissues: they generated more action potentials during a maximal depolarising current pulse (7 ± 1 compared to 1.6 ± 0.2); they had a smaller afterhyperpolarisation (9 ± 2 mV s compared to 20 ± 2 mV s); and they were more likely to receive fast excitatory synaptic input (74% compared to 17%), possess spontaneous activity (46% compared to 3%), and generate anodal break action potentials (58% compared to 19%). Although the resting membrane potential, input resistance and action potential characteristics were unaltered in AH neurones from inflamed tissues, they exhibited an enhanced Cs⁺-sensitive rectification of the current–voltage relationship. This suggests that the increase in excitability of AH neurones may involve a colitis-induced augmentation of the hyperpolarisation-activated cation current (I_h) in these cells. An increased excitability, selectively in AH neurones, suggests that the afferent limb of intrinsic motor reflexes is disrupted in the inflamed colon and this may contribute to dysmotility associated with inflammatory diseases.