PREJUNCTIONAL MODULATION OF THE NITRERGIC INNERVATION OF THE CANINE ILEOCOLONIC JUNCTION VIA POTASSIUM CHANNELS

1 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. 2 The non-selective blockers of K channels, 4-aminopyridine (4-AP) and tetraethylammonium (TEA) and the blocker of large conductance Ca2+-activated K+ channels, charybdotoxi n, potently enhanced the NANC relaxations induced by low frequency sti mulation. The blocker of small conductance Ca2+-activated K+ channels, apamin, had no effect on electrically-induced NANC relaxations. 3 NAN C nerve-mediated relaxations induced by adenosine 5'-triphosphate (ATP ), acetylcholine (ACh) and gamma-aminobutyric acid (GABA) were signifi cantly enhanced by 4-AP and charybdotoxin but not by apamin. TEA signi ficantly enhanced the NANC relaxations in response to GABA and ATP whi le that in response to ACh was abolished. 4 None of the K+ channel blo ckers had an effect on the dose-response curve to NO, on the noradrena line-induced contraction or on the relaxation to nitroglycerine (GTN). 5 From these results we conclude that inhibition of prejunctional Kchannels increases the nitrergic relaxations induced by electrical and chemical receptor stimulation of NANC nerves and thus suggests a regu latory role for these prejunctional K+ channels in the release of NO f rom NANC nerves in the canine ileocolonic junction.