Activation of delayed rectifier potassium channels in canine proximal colon by vasoactive intestinal peptide.
1. Vasoactive intestinal peptide (VIP) inhibits phasic contractions and tone of gastrointestinal smooth muscles. This study examines electrical mechanisms that may mediate the inhibitory actions of VIP. 2. Electrical slow waves were recorded from canine proximal colon circular muscles. VIP (0.1 microM) decreased basal slow wave frequency but had no effect on amplitude or duration. When slow waves were enhanced with Bay K 8644 (1 microM), VIP decreased slow wave duration and inhibited contractions. 3. VIP inhibited slow waves and phasic contractions stimulated by tetraethylammonium chloride (TEA; 10 mM), but did not significantly reduce events stimulated by 4-amino-pyridine (4-AP; 10 mM). 4. Whole-cell outward currents were recorded from isolated myocytes, using the amphotericin B perforated patch technique. VIP (1 microM) increased charybdotoxin-insensitive outward currents. 5. Single voltage-dependent K+ channels were recorded in cell-attached patches. VIP increased reversibly the open probability, mean open time and mean burst duration of 4-AP-sensitive, charybdotoxin-insensitive K+ channels (KDR1). Two additional 4-AP- and charybdotoxin-insensitive K+ channels (approximately 90 pS and < 4 pS) were also observed in these patches, but were not significantly affected by VIP. 6. In summary, the effects of VIP on electrical slow waves may be due, in part, to activation of 4-AP-sensitive, 'delayed rectifier' K+ channels. Activation of these channels may contribute to premature slow wave repolarization, reduced Ca2+ entry, and inhibition of contractile force.
Shuttleworth
C W
CW
Department of Physiology, University of Nevada, Reno 89557, USA.
Koh
S D
SD
Bayginov
O
O
Sanders
K M
KM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014660:Vasoactive Intestinal Peptide; D013395:Sucrose; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester