ACTIVATION OF DELAYED RECTIFIER POTASSIUM CHANNELS IN CANINE PROXIMALCOLON BY VASOACTIVE-INTESTINAL-PEPTIDE

1. Vasoactive intestinal peptide (VIP) inhibits phasic contractions an d tone of gastrointestinal smooth muscles. This study examines electri cal mechanisms that may mediate tile inhibitory actions of VIP. 2. Ele ctrical slow wares were recorded from canine proximal colon circular m uscles. VIP (0.1 mu M) decreased basal slow wave frequency but had no effect on amplitude or duration. When slow waves were enhanced with Ba y K 8644 (1 mu M), VIP decreased slow wave duration and inhibited cont ractions. 3. VIP inhibited slow waves and phasic contractions stimulat ed by tetraethylammonium chloride (TEA; 10 mM), but did not significan tly reduce events stimulated by 4-aminopyridine (4-AP; 10 mM). 4. Whol e-cell outward currents were recorded from isolated myocytes, using th e amphotericin B perforated patch technique. VIP (1 mu M) increased ch arybdotoxin-insensitive outward currents. 5. Single voltage-dependent K+ channels were recorded in cell-attached patches. VIP increased reve rsibly the open probability, mean open time and mean burst duration of 4-AP-sensitive, charybdotoxin-insensitive K+ channels (K-DR1). Two ad ditional 4-AP- and charybdotoxin-insensitive K+ channels (similar to 9 0 pS and <4 pS) were also observed in these patches, but were not sign ificantly affected by VIP. 6. In summary, the effects of VIP on electr ical slow waves may be due, in part, to activation of 4-AP-sensitive, 'delayed rectifier' K+ channels. Activation of these channels may cont ribute to premature slow ware repolarization, reduced Ca2+ entry, and inhibition of contractile force.