Three types of high-threshold K+ currents were recorded in isolated neurons of the snail Helix pomatia using a two-microelectrode voltage clamp technique: transient K+ current (I-A), delayed rectifier (I-KD) and Ca2+-dependent K+ current (I-K(Ca)). Vinpocetine (1-100 muM) applied to the bath affected different types of K+ current in different ways: I-A was increased (35 +/- 14%), I-KD was moderately inhibited (20 +/- 9%) and I-K(Ca) was strongly suppressed (45 +/- 15%). When I, and I,(,,) were present in the same cell, vinpocetine exerted a dual effect on the total K+ current, depending on the amplitude of the test stimulus. In the presence of vinpocetine, the I-V curve crossed the control I-V curve. The inhibition of I-K(Ca) by vinpocetine between 1 and 100 muM is unlikely to be a result of Ca2+ current (I-Ca) suppression, as the latter was inhibited only at vinpocetine concentrations exceeding 300 muM. Dibutyryl cyclic GMP (dbcGMP) (but not dbcAMP) mimicked the effects of vinpocetine in the majority of cells tested (coefficient of correlation r = 0.60, P < 0.05, n = 22). The data suggest that modulation of different types of Kf current in neuronal membrane can contribute, at least partially, to the nootropic effect of vinpocetine through the relation of intracellular Ca2+ concentration. (C) 2001 Elsevier Science Inc. All rights reserved.