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Second Messengers in the Presynaptic Regulation of Glycinergic Synapses in Frog Motoneurons

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The possible pathways mediating the inhibitory influences of two types of presynaptic metabotropic receptors – group III metabotropic glutamate receptors (mGluRIII) and GABAB receptors (GABABR) – on miniature glycinergic activity in motoneurons in the isolated spinal cord of the frog Rana ridibunda were studied. The glycinergic component is dominant in the inhibitory miniature activity of motoneurons [3]. Baclofen and LAP4, which are selective agonists of GABABR and mGluRIII, inhibited miniature glycinergic activity, decreasing frequency by 48.0 ± 5.6 (n = 8) and 48.5 ± 8.6% (n = 5), respectively. The amplitude of miniature potentials did not change significantly, which is evidence for a presynaptic mechanism of modulation of synaptic transmission. Studies of the stages in the mediation of the influences of the metabotropic receptors studied here on the process of glycine release from presynaptic terminals were performed by applying their selective agonists in conditions of previous selective blockade of the components mediating modulation of glycinergic synaptic transmission. The effects of mGluRIII were shown to be mediated tghe feedback via adenylate cyclase (AC), the next stage being mediated by protein kinase A (PKA), as their selective blockade virtually eliminated by effect of activation of mGluRIII. The effects of GABABR on miniature glycinergic activity did not involve AC activity, as its blocker SQ22536 did not alter the inhibitory effect of baclofen. The effects of GABABR were mediated by negative feedback via phospholipase C (PLC), as its prior exclusion (inhibitor U73122) prevented the effect of application of baclofen. However, the next possible stage in this pathway – protein kinase C (PKC) – did not have a role in mediating the influences of GABABR, as the PKC blocker (GF109302X) had no influences on the effect of baclofen. The common component in mediating the effects of mGluRIII and GABABR on miniature glycinergic activity may consist of inositol triphosphate receptors (IP3R), which regulate calcium release from intraterminal depots and, according to published data, are linked with both PKA or cAMP and with PLC. In our experiments, 2-APB, an IP3R antagonist, decreased miniature glycinergic activity frequency by 26 ± 8% (n = 7) and prevented the inhibitory effects of application of both mGluRIII and GABABR agonists. This stage of mediation of the influences of mGluRIII and GABABR appears to involve collision and interaction between these (crosstalk), as demonstrated by our previous studies [2].

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    O. A. Karamyan, N. M. Chmykhova & N. P. Veselkin

  2. St. Petersburg State University, St. Petersburg, Russia

    N. P. Veselkin

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  1. O. A. Karamyan
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  2. N. M. Chmykhova
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  3. N. P. Veselkin
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Correspondence to N. P. Veselkin.

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Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 102, No. 9, pp. 1099–1110, September, 2016.

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Karamyan, O.A., Chmykhova, N.M. & Veselkin, N.P. Second Messengers in the Presynaptic Regulation of Glycinergic Synapses in Frog Motoneurons. Neurosci Behav Physi 48, 166–173 (2018). https://doi.org/10.1007/s11055-018-0547-y

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