Aminopyridines enhance opening of calcium-activated potassium channels in GH3 anterior pituitary cells

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Abstract

The effects of aminopyridine analogs in 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 >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 indirecty, possibly as a result of an increase in the effective intracellular free Ca2+ level.

Original languageEnglish (US)
Pages (from-to)458-468
Number of pages11
JournalMolecular Pharmacology
Volume35
Issue number4
StatePublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology

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