Prejunctional modulation of the nitrergic innervation of the canine ileocolonic junction via potassium channels

Abstract

The effects of different K+ channel blockers were studied on nitric oxide (NO)‐mediated non‐adrenergic non‐cholinergic (NANC) relaxations in the canine ileocolonic junction. The non‐selective blockers of K+ channels, 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA) and the blocker of large conductance Ca2+‐activated K+ channels, charybdotoxin, potently enhanced the NANC relaxations induced by low frequency stimulation. The blocker of small conductance Ca2+‐activated K+ channels, apamin, had no effect on electrically‐induced NANC relaxations. NANC nerve‐mediated relaxations induced by adenosine 5′‐triphosphate (ATP), acetylcholine (ACh) and γ‐aminobutyric acid (GABA) were significantly enhanced by 4‐AP and charybdotoxin but not by apamin. TEA significantly enhanced the NANC relaxations in response to GABA and ATP while that in response to ACh was abolished. None of the K+ channel blockers had an effect on the dose‐response curve to NO, on the noradrenaline‐induced contraction or on the relaxation to nitroglycerine (GTN). From these results we conclude that inhibition of prejunctional K+ channels increases the nitrergic relaxations induced by electrical and chemical receptor stimulation of NANC nerves and thus suggests a regulatory role for these prejunctional K+ channels in the release of NO from NANC nerves in the canine ileocolonic junction. 1993 British Pharmacological Society