Changes in intracellular potentials and ionic currents of the mollusk and activity of Cl--channels under exposure to some inhibitory amino acids and new litium-containing compounds of them

Abstract

The Changes of membrane rest potential (RP), action potential (AP), impulse activity (IA) as well as sodium, calcium and potassium ionic currents in neurons of isolated central nervous system of the Planorbarius corneus mollusk (pedal ganglia) under the extracellular action of inhibitory amino acids GABA, glycine and β-alanine and their litium-containing derivatives (LCD) in 0.1, 1 and 5 mM concentrations have been studied using a microelectrode technique. They induced the same dose-dependent and irreversible depolarization of neurons on 2-10 mV accompanied by increase of AP frequency, prolongation of their duration and decrease of summmerized ionic currents (dV/dt). According to degree of depolarization, the drugs were placed in the following range in decreasing activity: compound 3 > compound 2 > compound 1. In identified pedal ganglion neurons (PPed1), compound 3 in contrast to other compounds induced hyperpolarization by 2-10 mV and blocked impulse activity. The amplitude of sodium and calcium channels was decreased by 7-15 %, in the same degree after application of all compounds exposed in concentration of 5 mM. Efflux potassium ionic currents were increased in dose-dependent manner and irreversibly about by 3-7 % assessed on amplitude indexes without changes in kinetic parameters after application of LCD. Therefore, the decrease of ionic current amplitudes was due to both depolarization of neurons and direct action of LCD on ionic channels. Thus, LCD possess membranotropic activity and can modulate functional state of neurons. In the study of chloride channels in cells culture of rat glioma C6 in vitro by patch-clamp method, GABA, glycine, β-alanine and their LCD 10 µM/l activated chloride channels, shifting equiliblium membrane potential of glioma cells from -90… -70 mV to -55... -60 mV. All compounds (transmitters and LCD) were placed in the following range: glycine > GABA > β-alanine and compound 1 > compound 3 > compound 2 according to descending activity. Therefore, the most active compounds activating Cl--channels were glycine and compound 1 (LCD). Glycine was shown to be coagonist GABA receptors and its litium salt possessed significant membranotropic activity.