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 (I-Ca) and three subtypes of the outward voltage-gated K+ current were recorded: Ca2+-dependent K+ current (I-K(Ca)), delayed rectifying current (I-KD), and fast-inactivating K+ current (I-A). It has been found that I-Ca was not changed in the presence of 30 pm vinpocetine, 100 mum piracetam or 10 nm GVS-111, while slow-inactivating, TEA-sensitive I-K(CA) and I-KD were inhibited more strongly than In contrast, the fast-inactivating, 4-AP-sensitive K+ current (I-A) was not diminished by low concentrations of piracetam and GVS-111, while vinpocetine ever augmented it, A possible role of slow-inactivating subtypes of the K+ channels in the development of different forms of dementia is discussed.