In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 20, No. 15 ( 2000-08-01), p. 5654-5662
Abstract:
Recent genetic analyses have revealed an important association of the gene encoding the P/Q-type voltage-dependent Ca 2+ channel α 1A subunit with hereditary neurological disorders. We have identified the ataxic mouse mutation, rolling Nagoya ( tg rol ), in the α 1A gene that leads to a charge-neutralizing arginine-to-glycine substitution at position 1262 in the voltage sensor-forming segment S4 in repeat III. Ca 2+ channel currents in acutely dissociated Purkinje cells, where P-type is the dominant type, showed a marked decrease in slope and a depolarizing shift by 8 mV of the conductance–voltage curve and reduction in current density in tg rol mouse cerebella, compared with those in wild-type. Compatible functional change was induced by the tg rol mutation in the recombinant α 1A channel, indicating that a defect in voltage sensor of P/Q-type Ca 2+ channels is the direct consequence of the tg rol mutation. Furthermore, somatic whole-cell recording of mutant Purkinje cells displayed only abortive Na + burst activity and hardly exhibited Ca 2+ spike activity in cerebellar slices. Thus, in tg rol mice, reduced voltage sensitivity, which may derive from a gating charge defect, and diminished activity of the P-type α 1A Ca 2+ channel significantly impair integrative properties of Purkinje neurons, presumably resulting in locomotor deficits.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.20-15-05654.2000
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
2000
detail.hit.zdb_id:
1475274-8
SSG:
12
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