Bulletin of Experimental Biology and Medicine, Vol. 156, No. 6, April, 2014 PHYSIOLOGY

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Changes in Intracellular Potentials of Snail Neurons Induced by -Phenylglutamic Acid Hydrochloride

A. I. Vislobokov, Yu. D. Ignatov, V. V. Bagmetova*, and I. N. Tyurenkov* Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 156, No. 12, pp. 672-676, December, 2013 Original article submitted December 4, 2012 β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutamine, or glutarone) in concentrations of 1, 10, 100, and 1000 μM reversibly and dose-dependently modulated the intracellular action potentials in Plantorbarius corneus snail neurons and hyperpolarized the membrane by 9.1±2.5% with maximum shift of resting potential at 100 μM. Hyperpolarization was accompanied by up-regulation of synaptic activity and changes in the pattern of impulse activity manifested by a decrease in the discharge rate, shortening of the interburst time, increase in the mean number of spikes in the bursts, and shortening of the interspike time within the bursts. Both hyperpolarization and impulse activity rearrangement persisted for 10-20 min after washing of RGPU-135. Key Words: glutamic acid derivatives; β-phenylglutamic acid hydrochloride; Plantorbarius corneus; resting potential; impulse activity A novel derivative of glutamic acid, β-phenylglutamic acid hydrochloride (RGPU-135, glutarone, neuroglutamine) demonstrates a peculiar profile of pharmacological activity: pronounced antidepressant action is accompanied by anxiolytic and neuroprotective effects as well as with nootropic, activating, and immunostimulating properties [7], low toxicity and potentially high drug safety [2]. The preclinical study of specific activity and drug safety of RGPU-135 is coming to the end, although the mechanisms of its action are not entirely clear. Similar to other psychotropic agents, the neuropsychotropic effect of RGPU135 could be mediated not only via the infl uence on cerebral neurotransmitter systems, but also via changes in electrical excitability of the nervous tissue [1,9,11] and activity of ionic channels in the neuronal membrane [4-6,8-12]. Our aim was to examine the effect of RGPU-135 on the neurons, which can mediate its systemic effects via changing their electrical activity. I. P. Pavlov St. Petersburg State Medical University; *Volgograd State Medical University, Russia. Address for correspondence: [email protected]. A. I. Vislobokov

MATERIALS AND METHODS The study was carried out on giant (100-200 μ) neurons of the pedal and visceral ganglia in the circumesophageal complex of CNS of Plantorbarius corneus (Great Ramshorn) snail. The ganglionic neurons of this snail are colored and better seen under a binocular lens than similar neurons in pond snail. CNS was cut from the snail body and placed into a chamber (0.5 cm3) with physiological saline containing (in mM): 50 NaCl, 2 KCl, 2 CaCl2, 1.5 MgCl2, 10 Tris-OH, pH 7.5. Electrical activity of the neurons was recorded with glass microelectrodes (2.5 M KCl, 10-20 MΩ) [3,4]. RGPU-135 has been synthesized in the Chair of Organic Chemistry of A. I. Gertsen State Pedagogic University. The substance was dissolved in physiological saline to final concentrations of 1, 10, 100, and 1000 μM. The effects of extracellular application of RGPU-135 on electrical activity of neurons were assessed by the changes in their resting potential (RP), impulse activity (IA), and amplitude of action potentials (AP). The signals were digitized with an L-791 A/D converter (L-Card, Russia).

0007-4888/14/15660717 © 2014 Springer Science+Business Media New York

Bulletin of Experimental Biology and Medicine, Vol. 156, No. 6, April, 2014 PHYSIOLOGY

718

Fig. 1. Concentration-dependent effect of RGPU-135 on the electrical parameters of neurons in Plantorbarius corneus snail. a) The changes in RP (n=18); b) The changes in RP, AP amplitude, and IA of LPe1 neuron: 1) control; 2) RGPU-135 (1 μM); 3) 10 μM; 4) 100 μM; 5) 1000 μM; 6) washing. Abscissa: concentration (a) or time (b, 1 box is 1 min). Ordinate: a) RP is given in percentage to control; p

Changes in intracellular potentials of snail neurons induced by β-phenylglutamic acid hydrochloride.

β-Phenylglutamic acid hydrochloride (RGPU-135, neuroglutamine, or glutarone) in concentrations of 1, 10, 100, and 1000 μM reversibly and dose-dependen...
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