CHARACTERIZATION OF AN OUTWARD POTASSIUM CURRENT IN CANINE JEJUNAL CIRCULATION SMOOTH-MUSCLE AND ITS ACTIVATION BY FENAMATES

1. A perforated patch clamp technique was used to study an outward pot assium current in freshly dissociated circular smooth muscle cells of the canine jejunum. 2. A voltage-dependent outward current was identif ied which was highly potassium selective, weakly holding voltage sensi tive, increased its open probability at - 65 mV, and reached unit open probability at + 5 mV. 3. Quinidine (0.1-1 mm) and tetraethylammonium ion (TEA) (10-50 mm), blocked the potassium current in a dose-depende nt manner. Blockade of the outward potassium current was accompanied b y membrane depolarization which reversed on removal of the blocker fro m the bathing solution. 4. Mefenamic and flufenamic acids, non-steroid al anti-inflammatory agents in the fenamate group, were potent activat ors of the current. Activation was accompanied by hyperpolarization of the membrane with a mean shift in the membrane voltage of 22 mV. 5. I t was concluded that the outward potassium current is a major regulato r of the resting membrane voltage in isolated circular smooth muscle c ells of the canine jejunum. Fenamates activated this current with pote ntially profound effects on cellular excitability.