Abstract: | In experiments on isolated spinal cord of young rats 7–14 days old under conditions of takeoff of the electrical activity of the spinal roots with a sugar bridge, it was established that the GABA-mimetic phenibut induces direct depolarization of the motoneurons. In the same concentration range (10–5-10–4 M), GABA has a dual effect. The depolarizing component of the action of GABA in part of the experiments and the depolarizing effect of phenibut in all the experiments are preserved in the presence of picrotoxin (10–5 M) and under conditions of superfusion of the brain with a solution with a reduced chloride concentration. This depolarizing effect of phenibut, not associated with the activation of GABAA receptors and chloride channels coupled with them, is unchanged in a medium with Na+ deficiency, is enhanced during depolarization of the motoneurons due to an increased concentration of K+ (10 mM) and in the presence of imidazole, but is entirely eliminated in a medium with Ca2+ deficiency, containing 2 mM Mn2+, or in the presence of theophylline (10–4 M). It is suggested that phenibut, and to some degree, GABA lower the intracellular concentration of cAMP by means of activation of the GABAB receptors, which leads to blocking of the functional activity of the potential-dependent calcium channels and a decrease in the calcium-activated outflowing potassium currents. The ability to weaken the inflowing calcium currents may also be the basis of the presynaptic inhibiting effect of GABA and GABA-mimetics (phenibut, baclofen, etc.) on the pulsed release of mediators by the axon terminals of catecholaminergic, glutamatergic, and GABA-ergic neurons.A. M. Gor'kii Donetsk Medical Institute. Translated from Neirofiziologiya, Vol. 17, No. 4, pp. 481–489, July–August, 1985. |