Reduced voltage sensitivity of activation of P/Q-type Ca2+ channels is associated with the ataxic mouse mutation rolling Nagoya (tg(rol)).
J Neurosci
; 20(15): 5654-62, 2000 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-10908603
ABSTRACT
Recent genetic analyses have revealed an important association of the gene encoding the P/Q-type voltage-dependent Ca(2+) channel alpha(1A) subunit with hereditary neurological disorders. We have identified the ataxic mouse mutation, rolling Nagoya (tg(rol)), in the alpha(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 alpha(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 alpha(1A) Ca(2+) channel significantly impair integrative properties of Purkinje neurons, presumably resulting in locomotor deficits.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Purkinje Cells
/
Ataxia
/
Calcium Channels, N-Type
Type of study:
Diagnostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Neurosci
Year:
2000
Document type:
Article
Affiliation country:
Japan