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Background  Alternative splicing of low-voltage-activated T-type calcium channels contributes to the molecular and functional diversity mediating complex network oscillations in the normal brain. Transcript scanning of the human  CACNA1G  gene has revealed the presence of 11 regions within the coding sequence subjected to alternative splicing, some of which enhance T-type current. In mouse models of absence epilepsy, elevated T-type calcium currents without clear increases in channel expression are found in thalamic neurons that promote abnormal neuronal synchronization. To test whether enhanced T-type currents in these models reflect pathogenic alterations in channel splice isoforms, we determined the extent of alternative splicing of mouse  Cacna1g  transcripts and whether evidence of altered transcript splicing could be detected in mouse absence epilepsy models.    Results  Transcript scanning of the murine  Cacna1g  gene detected 12 regions encoding alternative splice isoforms of Ca v 3.1/α1G T-type calcium channels. Of the 12 splice sites, six displayed homology to the human  CACNA1G  splice sites, while six novel mouse-specific splicing events were identified, including one intron retention, three alternative acceptor sites, one alternative donor site, and one exon exclusion. In addition, two brain region-specific alternative splice patterns were observed in the cerebellum. Comparative analyses of brain regions from four monogenic absence epilepsy mouse models with altered thalamic T-type currents and wildtype controls failed to reveal differences in  Cacna1g  splicing patterns.    Conclusion  The determination of six novel alternative splice sites within the coding region of the mouse  Cacna1g  gene greatly expands the potential biophysical diversity of voltage-gated T-type channels in the mouse central nervous system. Although alternative splicing of Ca v 3.1/α1G channels does not explain the enhancement of T-type current identified in four mouse models of absence epilepsy, post-transcriptional modification of T-type channels through this mechanism may influence other developmental neurological phenotypes.

Expanded alternative splice isoform profiling of the mouse Cav3.1/α1G T-type calcium channel