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

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.