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

• DOI: 10.1016/j.neuron.2006.09.035
• Publication Date: 2006-11-27T14:57:23Z
• Authors: Klaus Hirzel; Ulrike Müller; A. Tobias Latal; Swen Hülsmann; Joanna Grudzinska; Mathias W. Seeliger; Heinrich Betz; Bodo Laube
• Keywords: Male; 0301 basic medicine; 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

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.