Selective suppression of the slow-inactivating potassium currents by nootropics in molluscan neurons.
The role of the voltage-gated K+ channels in the effect of some nootropics was investigated. Earlier, the multiple effect of high concentrations of two nootropics, piracetam and its peptide analogue GVS-111 [Seredenin et al. (1995), US Patent No. 5,439,930], on Ca2+ and K+ currents of molluscan neurons was shown [Solntseva et al. (1997), General Pharmacology 29, 85-89]. In the present work, we describe the selective effect of low concentrations of these nootropics as well as vinpocetine on certain types of K+ current. The experiments were performed on isolated neurons of the land snail Helix pomatia using a two-microelectrode voltage-clamp method. The inward voltage-gated Ca2+ current (ICa) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (IK(Ca)), delayed rectifying current (IKD), and fast-inactivating K+ current (IA). It has been found that I Ca was not changed in the presence of 30 microM vinpocetine, 100 microM piracetam or 10 nM GVS-111, while slow-inactivating, TEA-sensitive IK(Ca) and IKD were inhibited (IK(Ca) more strongly than IKD). In contrast, the fast-inactivating, 4-AP-sensitive K+ current (IA) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine even augmented it. A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002469:Cell Separation; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006372:Helix, Snails / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010889:Piracetam / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated; D014748:Vinca Alkaloids / Q000494:pharmacology
D015220:Calcium Channels; D004151:Dipeptides; D018697:Nootropic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D014748:Vinca Alkaloids; C059983:potassium channel protein I(sk); C103871:ethyl phenylacetyl-Pro-Gly; C013983:vinpocetine; D010889:Piracetam