Mechanism of cyclic AMP-induced hyperpolarization in canine colon.
The mechanism of forskolin (FSK)-induced hyperpolarization was investigated in strips of canine colonic circular muscle. FSK responses were compared to those of the K+ channel opener lemakalim (LEM). Both FSK (10 microM) and LEM (10 microM) hyperpolarized cells near the myenteric border by 10 to 20 mV. Responses to both agents were abolished by 35 mM external K+, indicating a probable mediation by K+ channels. FSK increased the open probability of Ca(++)-activated K+ channels in isolated colonic myocytes. However, in muscle strips charybdotoxin (100 nM) and tetraethylammonium (10 mM) failed to reduce FSK- and LEM-induced hyperpolarizations whereas tetrapentylammonium (50 microM) and 4-aminopyridine (10 mM) blocked both responses. Phencyclidine (100 microM), Ba++ (1 mM) and the antagonist of ATP-sensitive K+ currents glybenclamide (10 microM) blocked LEM- but not FSK-induced hyperpolarizations. Delayed rectifier current in isolated myocytes was activated near -20 mV and was blocked by (order of potency): nifedipine > tetrapentylammonium > phencyclidine > 4-aminopyridine > tetraethylammonium. Charybdotoxin (100 nM), Ba++ (1 mM) and glybenclamide (10 microM) were without effect. Ca(++)-activated K+ current was activated near +30 mV and was blocked by: charybdotoxin > tetraethylammonium > tetrapentylammonium >> phencyclidine = 4-amino-pyridine. These data suggest that LEM induces membrane hyperpolarization by activation of a K+ current with a pharmacology similar to ATP-sensitive K+ current whereas cyclic AMP-induced hyperpolarization appears to involve activation of a current other than delayed rectifier current, Ca(++)-activated K+ current or ATP-sensitive K+ current.
Du
C
C
Department of Physiology, University of Nevada, Reno.
Carl
A
A
Smith
T K
TK
Sanders
K M
KM
Keef
K D
KD
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D019806:Cromakalim; D000242:Cyclic AMP / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D005576:Colforsin; D000242:Cyclic AMP; D002118:Calcium