Original ArticleIdentification and Cloning of Putative Human Neuronal Voltage-Gated Calcium Channel γ-2 and γ-3 Subunits: Neurologic Implications
Section snippets
Computerized Analysis of GenBank and MEDLINE Databases
Because several channelopathies have been identified in hereditary seizure disorders of humans and mice,3, 4, 5, 6, 7, 8, 9, 10 we used the National Center for Biotechnology Information (NCBI) Gapped BLAST11 search program to look for human homologues for the recently described mouse γ-2 sequence.1 We used the NCBI programs Electronic PCR12 and Map Search13, 14 to localize amino acid sequences of interest to specific chromosomal regions, and a software program called TMpredict15 was used to
RESULTS
Using a cDNA library derived from adult human cerebellum RNA, we cloned and fully sequenced the human γ-2 cDNA noted by Letts and associates1 as a partial sequence on chromosome 22 (GenBank accession numbers Z83733 and AL022313). We then used the amino acid sequence that Letts and colleagues1 established for the mouse γ-2 subunit to identify, by computer-assisted searching of NCBI resources, a previously unrecognized homologous sequence from Homo sapiens on chromosome 16p12p13.1, which is
DISCUSSION
On the basis of this study, we conclude that heteromeric voltage-gated calcium channels in human neurons likely contain γ subunits in addition to their previously recognized a.I, α2-8, and ˜ subunits. Before publication of the report by Letts and associates,1 a γ subunit (γ-1) was recognized only in the dihydropyridine-sensitive L-type calcium channel found in skeletal muscle. Two genomic sequences that had been deposited in GenBank databases, and are the subject of this report (&gammal-2 noted
CONCLUSION
Further developmental, mutational, and immunologic studies of the human γ-2 and γ-3 neuronal calcium channel subunit genes are warranted. In particular, these genes merit surveillance for mutations in persons with familial infantile convulsions and paroxysmal choreoathetosis. The dominant γ subunit isoform expressed at various stages of development and in all brain regions should be determined as well because these genes may be preferentially expressed at different stages of development, as is
ACKNOWLEDGMENT
We thank Dr. Daniel J. McCormick, director of the Mayo Clinic Protein Core Facility, for performing amino acid sequence comparison and consensus analyses.
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This study was supported in part by funds from the Mayo Foundation (J.L.B.) and Grant CA 37343 from the National Cancer Institute (V.A.L).