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- W2038049156 abstract "Alternative splicing is known to generate multiple functionally distinct calcium channel variants that exhibit distinct spatial and temporal expression patterns. In humans, naturally occurring mutations in genes encoding calcium channel pore forming α1-subunits are associated with several severe hereditary disorders although it remains to be described whether there exists any relationship between the physiological effects of these mutations and calcium channel splice variation. In the present study, we systematically compare the biophysical effects of three type-1 familial hemiplegic migraine (FHM-1) mutations in two predominant splice variants of the neuronal CaV2.1 P/Q-type channel. All three FHM-1 mutations cause a greater hyperpolarizing shift in voltage-dependent properties when expressed in the short carboxyl terminus variant (CaV2.1 Δ47) compared to the long variant (CaV2.1 +47). Furthermore, the FHM-1 mutations also exhibit differential splice variant-specific effects on recovery from inactivation and accumulation of inactivation during tonic and burst firing. Our findings provide important insight concerning the role of calcium channel alternatively spliced variants and the molecular pathophysiology of FHM-1 and potentially of other calcium channelopathies." @default.
- W2038049156 created "2016-06-24" @default.
- W2038049156 creator A5001290070 @default.
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- W2038049156 date "2009-03-15" @default.
- W2038049156 modified "2023-10-16" @default.
- W2038049156 title "Ca<sub>V</sub>2.1 P/Q-type calcium channel alternative splicing affects the functional impact of familial hemiplegic migraine mutations: Implications for calcium channelopathies" @default.
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- W2038049156 doi "https://doi.org/10.4161/chan.3.2.7932" @default.
- W2038049156 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/19242091" @default.
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