Hyperekplexia Phenotype of Glycine Receptor α1 Subunit Mutant Mice Identifies Zn2+ as an Essential Endogenous Modulator of Glycinergic Neurotransmission

Male Neuroscience(all) HUMDISEASE Glycine Efferent Pathways MOLNEURO Cell Line Mice Mice, Neurologic Mutants 03 medical and health sciences Organ Culture Techniques Receptors, Glycine Animals Humans 0303 health sciences Chimera Neural Inhibition Mice, Mutant Strains Mice, Inbred C57BL Disease Models, Animal Phenotype SIGNALING Dystonic Disorders Mutation Female Brain Stem
DOI: 10.1016/j.neuron.2006.09.035 Publication Date: 2006-11-27T14:57:23Z
ABSTRACT
Zn2+ is thought to modulate neurotransmission by affecting currents mediated ligand-gated ion channels and transmitter reuptake Na+-dependent transporter systems. Here, we examined the in vivo relevance of neuromodulation producing knockin mice carrying mutation D80A glycine receptor (GlyR) α1 subunit gene (Glra1). This substitution selectively eliminates potentiating effect on GlyR currents. Mice homozygous for Glra1(D80A) develop a severe neuromotor phenotype postnatally that resembles forms human hyperekplexia (startle disease) caused mutations genes. In spinal neurons brainstem slices from mice, expression, synaptic localization, basal glycinergic transmission were normal; however, potentiation spontaneous was significantly impaired. Thus, due loss containing GlyRs, indicating essential proper functioning neurotransmission.
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