Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
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Target Concepts:
Gene/Protein
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Query: UMLS:C0040822 (
tremor
)
18,428
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Spinocerebellar ataxia (SCA) 42 is caused by a mutation in
CACNA1G
, which encodes the low voltage-gated calcium channel Ca
V
3.1 (T-type). Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting
tremor
, particularly head
tremor
. This symptom improved with the administration of low-dose of zonisamide (ZNS), a T-type calcium channel blocker effective for treating Parkinson's disease and epilepsy. Previous electrophysiological studies showed that the voltage dependence of this mutant Ca
V
3.1 was shifted toward the positive potential. This abnormal shift was considered a factor related to disease onset and symptoms. In this study, we performed whole-cell recordings of GFP-expressing HEK293T cells that expressed wild-type or mutant Ca
V
3.1 and investigated the changes in the abnormal shift of voltage dependence of the mutant Ca
V
3.1. The results showed that ZNS in an amount equivalent to the patient's internal dose significantly ameliorated the abnormal shift in the mutant Ca
V
3.1, giving values close to those in the wild-type. On the other hand, ZNS did not affect the voltage dependence of wild-type Ca
V
3.1. Because Ca
V
3.1 is known to be involved in tremogenesis, modulation of the voltage dependence of mutant Ca
V
3.1 by ZNS might have contributed to improvement in the intractable
tremor
of our patient with SCA42. Moreover, efonidipine, another T-type calcium channel blocker, had no effect on tremors in our patient with SCA42 and did not improve the abnormal shift in the voltage dependence of the mutant Ca
V
3.1. This indicates that ZNS is distinct from other T-type calcium channel blockers in terms of modulation of the voltage dependence of the mutant Ca
V
3.1.
...
PMID:Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel Ca
V
3.1 caused by a mutation responsible for spinocerebellar ataxia. 3324 96
