Effects of modulators of Ca(2+)-activated, intermediate-conductance potassium channels on motility of the rat small intestine, in vivo.
The movements of the intestine shift between different motor patterns, including between propulsion and mixing, but there is little information concerning mechanisms that may lead to changes in the patterns of motility. We have investigated the influence on intestinal motility of drugs that affect the after-hyperpolarization potential (AHP) of intrinsic primary afferent neurons (IPANs). The current of the AHP is carried by the intermediate conductance, calcium-activated, potassium (IK) channel. In anaesthetized rats, the IK channel blocker, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (0.05-1 mg kg(-1), i.v.) disrupted the regular propulsive pressure waves that occur in the small intestine and reduced propulsion of the contents (after 1 mg kg(-1), the fluid propelled was <25% of control). If the propulsion in the intestine was regular, the IK channel opener, 5,6-dichloro-1-ethyl-2-benzimidazolinone (DC-EBIO, 0.1 mg kg(-1) h(-1)) had no effect. DC-EBIO (0.1 mg kg(-1) h(-1)) restored propulsive activity after the nitric oxide synthase inhibitor, Nomega-nitro-l-arginine had changed motility to a mixing pattern. We suggest that the AHP determines the synchrony of action potential firing in synaptically coupled IPANs, and that this synchrony influences the patterns of firing of muscle motor neurons, and hence the pattern of contraction of the muscle and whether the pattern is predominantly propulsive or predominantly mixing.
Ferens
D
D
Department of Anatomy and Cell Biology and Centre for Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
Baell
J
J
Lessene
G
G
Smith
J E
JE
Furness
J B
JB
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000502:physiology*; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000378:metabolism / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
C507351:5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011720:Pyrazoles; C411671:TRAM 34; D019335:Nitroarginine