title: Aminopyridines enhance opening of calcium-activated potassium channels in GH3 anterior pituitary cells.
abstract: The effects of aminopyridine analogs on Ca2+-activated K+ channels in GH3 clonal anterior pituitary cells were studied using whole-cell voltage-clamp and single-channel recording techniques. Step depolarization from a holding potential of -50 mV activated a noninactivating, tetraethylammonium- and Cd2+-sensitive outward current. Tail current analysis indicated that this sustained outward current is carried predominantly by K+ ions. Extracellular perfusion with 4-aminopyridine and 3,4-diaminopyridine (0.05-5 mM) caused a dose-dependent enhancement of the outward current by up to 100 and 170%, respectively. This effect typically occurred with prolonged depolarizations of greater than 1-2 sec. Patch-clamp recordings in the cell-attached configuration demonstrated that 4-aminopyridine (2 mM) promotes the activity of a large-conductance (150-175 pS; 50-135 mM external K+), tetraethylammonium-sensitive, Ca2+-activated K+ channel; the drug had no effect on these channels in excised patches. These results indicate that aminopyridines enhance the opening of Ca2+-activated K+ channels in GH3 cells. Several lines of evidence suggest that this effect may occur indirectly, possibly as a result of an increase in the effective intracellular free Ca2+ level.
authors.affiliation: Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
authors.forename: M A
authors.initials: MA
authors.lastname: Rogawski
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D004553:Electric Conductivity; D008564:Membrane Potentials; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: D000631:Aminopyridines; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002104:Cadmium; D019789:Tetraethylammonium; D011188:Potassium; D002118:Calcium