Synaptic function and modulation of glycine receptor channels in the hypoglossal nucleus |
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Authors: | P Bregestovski M Mukhtarov |
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Institution: | (1) Institut de Neurobiologie de la Mediterranee (INMED), INSERM U29, Marseille, France |
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Abstract: | In this review, we discuss the function and modulation of chloride-selective glycine receptor (GlyR) channels, some genetic
diseases originated from dysfunction of GlyRs, and modulation of glycinergic synapses by intracellular calcium (Ca2+) with particular attention on the motoneurons of the hypoglossal nucleus. This motor nucleus is a brainstem structure implicated
in the command of coordinated movements during oral behavioral phenomena, including feeding, drinking, grooming, and respiration.
In this nucleus, more than 90% of its cells are motoneurons. These hypoglossal motoneurons (HMs) are involved in a variety
of motor functions and exhibit two remarkable features: (i) a low endogenous Ca2+ buffering capacity, which determines the rapid dynamics of cytosolic intracellular Ca2+, and (ii) powerful glycinergic inputs, which determine the main inhibitory drive on the above cells in adult animals. Glycine
receptors belong to the superfamily of Cys-loop ligand-gated ion channels. They are capable of forming functional homo-or
heteromeric chloride-selective channels. Dysfunction of GlyRs results in a genetic neurological motor disorders, including
hyperekplexia. These diseases originate from mutations in the GlyR gene, leading to a decrease in single channel conductance,
a lower affinity to the neurotransmitter, or a low level of GlyR expression. The function of glycinergic synapses is modulated
during developmental changes and strictly controlled by several feedback mechanisms at pre-and post-synaptic levels. The developmental
modulation consists in switch in the GlyR subunit composition and change in the chloride homeostasis during the synaptic maturation
and formation of inhibitory networks. Retrograde signalling plays an important role in the synaptic function of HMs; it provides
post-synaptic neurons with efficient tools for controlling pre-synaptic afferents. Glycine receptors and glycinergic synapses
are also regulated by intracellular Ca2+. The mechanisms of these modulations are discussed.
Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 338–349, July–October, 2007. |
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Keywords: | ligand-gated channels hypoglossal motoneurons hyperekplexia patch-clamp recording intracellular calcium retrograde signaling |
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