nystatin-a1 and cyclothiazide

Responses to glutamate receptor agonists were recorded from identified relay neurons in the dorsal lateral geniculate nucleus of the rat, using the nystatin-perforated patch-clamp technique. Rapid application of glutamate, N-methyl-D-aspartate, (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and kainate induced inward currents at a holding potential of -44 mV. The responses to low concentrations of each agonist were composed only of steady-state currents, but the responses to high concentrations were additionally composed of a rapid transient peak component except in the kainate-induced current. The currents induced by 10(-3)M N-methyl-D-aspartate in the external solution containing 0 mM Mg2+ and 10(-6)M glycine were reduced in amplitude when the external solution contained 1 mM Mg2+, and were abolished when the solution contained no glycine. The currents induced by a neurotransmitter candidate at retinogeniculate synapses, N-acetyl-aspartyl-glutamate, were markedly reduced in amplitude when the solution contained 1 mM Mg2+ or 10(-4)M DL-2-amino-5-phosphonovaleric acid. The current abolished in the Mg2+-containing, glycine-free solution (N-methyl-D-aspartate component) and the current remaining in the same solution (non-N-methyl-D-aspartate component) of the N-acetyl-aspartyl-glutamate response were both increased in a concentration-dependent manner, as the N-acetyl-aspartyl-glutamate concentration was increased. The current-voltage relationship of the currents induced by N-methyl-D-aspartate and N-acetyl-aspartyl-glutamate was characterized by Mg2+-dependent block at hyperpolarized potentials. The inward currents induced by 3 x 10(-4)M AMPA and 3 x 10(-4)M glutamate were markedly potentiated by 10(-4)M cyclothiazide, but the currents induced by 3 x 10(-4)M kainate and 10(-3)M N-acetyl-aspartyl-glutamate (non-N-methyl-D-aspartate component) were little affected. The currents induced by any agonist were not affected by 3 x 10(-4)g/ml concanavalin A. The current induced by 10(-4)M kainate was markedly suppressed by pretreatment with 10(-4)M AMPA or 10(-4)M glutamate, but only weakly by 10(-3)M N-acetyl-aspartylglutamate. The Ca2+ permeability (PCa/PCs) of the N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors was 9.57 and 0.16, respectively. These results suggest that dorsal lateral geniculate nucleus relay neurons of the rat possessed both Ca2+-permeable N-methyl-D-aspartate receptors and less permeable non-N-methyl-D-aspartate (

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Antihypertensive Agents; Benzothiadiazines; Concanavalin A; Dipeptides; Dose-Response Relationship, Drug; Excitatory Amino Acid Agonists; Geniculate Bodies; Glutamic Acid; Glycine; Ionophores; Kainic Acid; Membrane Potentials; N-Methylaspartate; Neurons; Neuroprotective Agents; Nystatin; Patch-Clamp Techniques; Rats; Rats, Wistar; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission