The concentration-clamp experiments with neurons isolated from the rat brain showed that nootropic and neuroprotective drug Semax added to perfusion solution at concentration of 1 μM augmented the amplitude of GABA-activated ionic currents in cerebellum Purkinje cells by 147±13%. In addition, Semax in perfusion solution (0.1 and 1 μM) diminished the amplitude of glycine-activated chloride currents in hippocampal pyramidal neurons down to 68 and 43% control level, respectively. Both potentiating and inhibitory effects developed slowly, and they were poorly reversible, which indicated a probable implication of second messengers in the observed phenomena. Semax accelerated the falling edge of glycine-activated current both after a short-term co-application with agonist and after addition of this peptide into perfusion solution.
Similar content being viewed by others
References
Ashmarin IP, Nezavibatko VN, Myasoedov NF, Kamensky AA, Grivennikov IA, Ponomareva-Stepnaya MA, Andreeva LA, Kaplan AY, Koshelev VB, Ryasina TV. Nootropic analogue of adrenocorticotropin 4-10-Semax: (the experience of design and investigation over 15 years). Zh. Vyssh. Nervn. Deyat. 1997;47(2):429-430. Russian.
V’unova TV, Shevchenko KV, Shevchenko VP, Bobrov MYu, Bezuglov VV, Myasoedov NF. Binding of Regulatory Neuropeptide [3H] Semax, Labeled in Terminal Pro, to Plasma Membranes of the Rat Forebrain. Neirokhimiya. 2006;23(1):57-62. Russian.
Gusev EI, Skvortsova VI, Myasoedov NF, Nezavibat’ko VN, Zhuravleva EYu, Vanichkin AV. Effectiveness of Semax in acute period of hemispheric ischemic stroke (clinical and electrophysiological study). Zh. Nevrol. Psikhiatr. 1997;96(6):26-54. Russian.
Gusev EI, Skvortsova VI, Chukanova EI. Semax in prevention of disease progress and development of exacerbations in patients with cerebrovascular insufficiency. Zh. Nevrol. Psikhiatr. 2005;105(2):35-40.
Shuvaev AN, Salmin VV, Kuvacheva NV, Pozhilenkova EA, Salmina AB. Modern tendencies in the development of the patchclamp technique: new opportunities for neuropharmacology and neurobiology. Annaly Klin. Eksp. Nevrol. 2015;9(4):54-58. Russian.
Catania A, Gatti S, Colombo G, Lipton JM. Targeting melanocortin receptors as a novel strategy to control inflammation. Pharmacol. Rev. 2004;56(1):1-29.
Clarkson AN, Huang BS, Macisaac SE, Mody I, Carmichael ST. Reducing excessive GABA-mediated tonic inhibition promotes functional recovery after stroke. Nature. 2010;468:305-309.
Cone RD. Anatomy and regulation of the central melanocortin system. Nat. Neurosci. 2005;8(5):571-578.
Giuliani D, Ottani A, Neri L, Zaffe D, Grieco P, Jochem J, Cavallini GM, Catania A, Guarini S. Multiple beneficial effects of melanocortin MC4 receptor agonists in experimental neurodegenerative disorders: Therapeutic perspectives. Prog. Neurobiol. 2017;148:40-56.
Hiu T, Farzampour Z, Paz JT, Wang EH, Badgely C, Olson A, Micheva KD, Wang G, Lemmens R, Tran KV, Nishiyama Y, Liang X, Hamilton SA, O’Rourke N, Smith SJ, Huguenard JR, Bliss TM, Steinberg GK. Enhanced phasic GABA inhibition during the repair phase of stroke: a novel therapeutic target. Brain. 2016;139(Pt 2):468-480.
Lilly SM, Zeng XJ, Tietz EI. Role of protein kinase A in GABAA receptor dysfunction in CA1 pyramidal cells following chronic benzodiazepine treatment. J. Neurochem. 2003;85(4):988-998.
McDonald BJ, Amato A, Connolly CN, Benke D, Moss SJ, Smart TG. Adjacent phosphorylation sites on GABAA receptor beta subunits determine regulation by cAMPdependent protein kinase. Nat. Neurosci. 1998;1(1):23-28.
Nusser Z, Sieghart W, Mody I. Differential regulation of synaptic GABAA receptors by cAMP-dependent protein kinase in mouse cerebellar and olfactory bulb neurones. J. Physiol. 1999;521(Pt 2):421-435.
Ono Y, Saitow F, Konishi S. Differential modulation of GABAA receptors underlies postsynaptic depolarization- and purinoceptor-mediated enhancement of cerebellar inhibitory transmission: a non-Stationary fluctuation analysis study. PLoS One. 2016;11(3):e0150636. doi: https://doi.org/10.1371/journal.pone.0150636.
Xu TL, Gong N. Glycine and glycine receptor signaling in hippocampal neurons: diversity, function and regulation. Prog. Neurobiol. 2010;91(4):349-361.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 11, pp. 564-569, November, 2017
Rights and permissions
About this article
Cite this article
Sharonova, I.N., Bukanova, Y.V., Myasoedov, N.F. et al. Modulation of GABA- and Glycine-Activated Ionic Currents with Semax in Isolated Cerebral Neurons. Bull Exp Biol Med 164, 612–616 (2018). https://doi.org/10.1007/s10517-018-4043-8
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-018-4043-8