The nootropic drug vinpocetine modulates different types of potassium currents in molluscan neurons.
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 microM) 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(A) and I(K(Ca)) 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 microM is unlikely to be a result of Ca2+ current (I(Ca)) suppression, as the latter was inhibited only at vinpocetine concentrations exceeding 300 microM. 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 K+ current in neuronal membrane can contribute, at least partially, to the nootropic effect of vinpocetine through the regulation of intracellular Ca2+ concentration.
Solntseva
E I
EI
Brain Research Institute, Russian Academy of Medical Sciences, per. Obukha 5, 103064, Moscow, Russia. soln@cc.nifhi.ac.ru
Bukanova
J V
JV
Skrebitsky
V G
VG
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000494:pharmacology; D004594:Electrophysiology; D008974:Mollusca; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018697:Nootropic Agents / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
D015220:Calcium Channels; D018697:Nootropic Agents; D015221:Potassium Channels; D014748:Vinca Alkaloids; C013983:vinpocetine; D003994:Bucladesine; D006152:Cyclic GMP