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.