New Tools Create Optogenetic Switch for G Proteins

By developing tools that enable light-dependent activation of ion channels by receptors in a range of different cell types, Brix Mücher and colleagues have provided researchers with the means to control G protein signaling in excitable cells. G protein-coupled receptors (GPCRs) that couple to members of the G_i/o family of G proteins activate GIRK channels, which suppress the activity of excitable cells, such as cardiomyocytes and neurons. Dysregulation of GIRK channels leads to the hyperexcitability of neurons and is implicated in mood disorders and epilepsy. In addition, age-related reductions in the amounts of G_i/o-coupled GPCRs in the brain are linked to various neurodegenerative diseases. Mücher et al. developed optogenetic constructs in an adenovirus-based expression system to express light-activated GPCRs together with target GIRK channel subunits in cell lines, cardiomyocytes, and cerebellar Purkinje neurons. As a result, light-induced activation of the GPCR resulted in robust activation of the GIRK channel, suppressing cellular activity. Together, these findings suggest that this system could be used therapeutically to restore control of cellular excitability and alleviate the symptoms associated with GIRK channel dysfunction.