Ionic mechanism of 4-aminopyridine action on leech neuropile glial cells

Extracellular 4-aminopyridine (4-AP), tetraethylammonium chloride (TEA) and quinine depolarized the neuropile glial cell membrane and decreased its in put resistance. As 4-AP induced the most pronounced effects, we focused on the action of 4-AP and clarified the ionic mechanisms involved. 4-AP did no t only block glial K+ channels, but also induced Na+ and Ca2+ influx via ot her than voltage-gated channels. The reversal potential of the 4-AP-induced current was -5 mV. Application of 5 mM Ni2+ or 0.1 mM d-tubocurarine reduc ed the 4-AP-induced depolarization and the associated decrease in input res istance. We therefore suggest that 4-AP mediates neuronal acetylcholine rel ease, apparently by a presynaptic mechanism. Activation of glial nicotinic acetylcholine receptors contributes to the depolarization, the decrease in input resistance, and the 4-AP-induced inward current. Furthermore, the 4-A P-induced depolarization activates additional voltage-sensitive K+ and Cl- channels and 4-AP-induced Ca2+ influx could activate Ca2+-sensitive K+ and Cl- channels. Together these effects compensate and even exceed the 4-AP-me diated reduction in K+ conductance. Therefore, the 4-AP-induced depolarizat ion was paralleled by a decreasing input resistance. (C) 1999 Elsevier Scie nce B.V. All rights reserved.