Potassium channel activation by cromakalim affects the slow wave type action potential of colonic smooth muscle.
The objective was to determine the existence of a glybenclamide-sensitive K+ conductance in intestinal smooth muscle, to study a possible role for this conductance in the generation of colonic slow wave type action potentials and to investigate if modification of this conductance could alter the action potentials and hence colonic motility. Intracellular electrical recording techniques were used to study properties of cells from the network of smooth muscle cells and interstitial cells of Cajal at the submucosal border of the circular muscle layer of the canine colon, where colonic pacemaker activity is generated. Cromakalim, dose dependently, hyperpolarized the cells and decreased the duration of the action potential, thereby inhibiting contractile activity. The upstroke amplitude and the action potential frequency remained unaltered. Glybenclamide did not affect any parameter of spontaneous electrical activity but prevented all effects of cromakalim. Cromakalim seems to act through increase in K+ conductance because the cromakalim-induced hyperpolarization is accompanied by a marked reduction in input resistance, is inhibited by glybenclamide and tetraethylammonium and it is shown that the cromakalim effect does not occur through effects on Na+ or Cl- conductances. Thus, glybenclamide-sensitive K+ conductance exists in colonic smooth muscle; the spontaneous development of slow wave type action potentials in this tissue occurs independent of this conductance. Its existence may provide pharmacological possibilities to affect gastrointestinal motility.
Farraway
L
L
Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada.
Huizinga
J D
JD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim; D004285:Dogs; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D005905:Glyburide