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.
Farrugia
G
G
Department of Physiology and Biophysics, Mayo Clinic, Rochester, MN 55905.
Rae
J L
JL
Szurszewski
J H
JH
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004285:Dogs; D004553:Electric Conductivity; D005260:Female; D005439:Flufenamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008528:Mefenamic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011802:Quinidine / Q000494:pharmacology; D012413:Rubidium / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D008528:Mefenamic Acid; D005439:Flufenamic Acid; D019789:Tetraethylammonium; D011802:Quinidine; D012413:Rubidium; D011188:Potassium; D002118:Calcium