Characterization of an outward potassium current in canine jejunal circular smooth muscle and its activation by fenamates.

1. A perforated patch clamp technique was used to study an outward potassium current in freshly dissociated circular smooth muscle cells of the canine jejunum. 2. A voltage‐dependent outward current was identified which was highly potassium selective, weakly holding voltage sensitive, 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‐dependent manner. Blockade of the outward potassium current was accompanied by membrane depolarization which reversed on removal of the blocker from the bathing solution. 4. Mefenamic and flufenamic acids, non‐steroidal anti‐inflammatory agents in the fenamate group, were potent activators of the current. Activation was accompanied by hyperpolarization of the membrane with a mean shift in the membrane voltage of 22 mV. 5. It was concluded that the outward potassium current is a major regulator of the resting membrane voltage in isolated circular smooth muscle cells of the canine jejunum. Fenamates activated this current with potentially profound effects on cellular excitability.