Action of cromakalim on potassium membrane conductance in isolated heart myocytes of frog.
1. The effects of cromakalim on membrane currents were studied at 20 degrees C in frog atrial and ventricular cells in patch clamp recording using the whole cell configuration. 2. When cromakalim (1 microM) was applied in the external medium, a time-independent current was activated in a few minutes. Cromakalim induced a weak increase of inward membrane currents recorded during hyperpolarization and a large increase of outward membrane currents recorded during depolarization. 3. The current voltage relationship of the cromakalim-induced current reversed near EK and rectified in the outward direction. 4. The cromakalim-activated current was inhibited by external application of cesium (20 mM), barium (1.8 mM), tolbutamide (1 mM) and glibenclamide (1 microM). 5. The effects of cromakalim were insensitive to a cytosolic increase in adenosine 5'-triphosphate (ATP, 3-5 mM). Cromakalim had no effects when applied in the cell. 6. Our results confirm that cromakalim activates an IK(ATP)-like conductance and suggest that the effects of the drug are due to an action on the external side of the membrane and are independent of the ATP cell content.
Pilsudski
R
R
Laboratoire de Physiologie des Eléments Excitables, CNRS UA244, Université Claude Bernard, Villeurbanne, France.
Rougier
O
O
Tourneur
Y
Y
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D002586:Cesium / Q000494:pharmacology; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects*; D011758:Pyrroles / Q000494:pharmacology*; D011893:Rana esculenta; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D013453:Sulfonylurea Compounds; D019806:Cromakalim; D002586:Cesium; D001464:Barium; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D005905:Glyburide