Patent ID: 10047377

Abstract:
Methods for modulating T-type calcium channel activity without directly targeting the T-type calcium channels are provided that include modulating kelch-like protein 1 (KLHL1) levels in a subject by providing a small hairpin RNA (shRNA) that targets a KLHL1 gene, and then administering the shRNA to the subject in an amount sufficient to modulate KLHL1 gene expression. The KLHL1 level directly effects current activity in T-type calcium channels and therefore modulation of KLHL 1 gene expression indirectly modulates current activity in T-type calcium channels. The methods may be implemented with, for example, an shRNA molecule suitable for modulating a KLHL1 level in the subject which may be provided as a plasmid encoding the shRNA molecule or an adeno-associated virus vector encoding the shRNA molecule. Methods of identifying compounds that modulate current activity in T-type calcium channels by determining an effect of the compound on KLHL1 gene expression are also provided.