GiRK2 and neuronal pattern of generation and settling in homozygous weaver mice
نویسندگان
چکیده
Correspondence: Joaquín Martí Unidad de Citología e Histología, Facultad de Biociencias, Universitat Autònoma de Barcelona, 08193 Barcelona, Spain Tel +34 9 3581 1666 Fax +34 9 3581 3357 email [email protected] Abstract: G-protein-activated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Several GIRK channel subunits have been found in the central nervous system. The weaver mutation has been identified as a single base-pair substitution in the gene encoding for a GIRK channel subunit, GIRK2. The cerebellum and the mesencephalon are predominately affected in the homozygous weaver mouse (wv/wv). In this article, we review our main findings about the patterns of cell generation, survival, and settling of two neuronal types in the wv/wv: Purkinje cells in the cerebellar cortex and dopaminergic neurons in the ventral midbrain. Moreover, we examine if the time of neuron origin determines the degree of cell vulnerability to the lethal action of mutated GIRK2. The possible involvement of other GIRK channel subunits is also considered within the context of earlier and more recent studies in the field.
منابع مشابه
Normal cerebellar development but susceptibility to seizures in mice lacking G protein-coupled, inwardly rectifying K+ channel GIRK2.
G protein-gated, inwardly rectifying K+ channels (GIRK) are effectors of G protein-coupled receptors for neurotransmitters and hormones and may play an important role in the regulation of neuronal excitability. GIRK channels may be important in neurodevelopment, as suggested by the recent finding that a point mutation in the pore region of GIRK2 (G156S) is responsible for the weaver (wv) phenot...
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The weaver (wv) gene (GIRK2) is a member of the G-protein-gated inwardly rectifying potassium (GIRK) channel family, known effectors in the signal transduction pathway of neurotransmitters such as acetylcholine, dopamine, opioid peptides, and substance P in modulation of neurotransmitter release and neuronal excitability. GIRK2 immunoreactivity is found in but not limited to brain regions known...
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متن کاملThe weaver mutation of GIRK2 results in a loss of inwardly rectifying K+ current in cerebellar granule cells.
The weaver mutation in mice results in a severe ataxia that is attributable to the degeneration of cerebellar granule cells and dopaminergic neurons in the substantia nigra. Recent genetic studies indicate that the GIRK2 gene is altered in weaver. This gene codes for a G-protein-activated, inwardly rectifying K+ channel protein (8). The mutation results in a single amino acid substitution (glyc...
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