The involvement of GIRK channels in epilepsy has been inferred from the phenotype of mice where a GIRK subunit has been deleted. GIRK2 knockout mice develop spontaneous convulsions and show a propensity for generalized seizures when injected with a pro-convulsive GABAA receptor antagonist145. Drugs such as desimipramine, fluoxetine, haloperidol, thioridazine, pimozide and clozapine146 (Supplemental Table S1) that are used for the treatment of various neurological disorders, may inhibit GIRK channels and hence cause seizures, a known side effect of these drugs. On the other hand, electroconvulsive shock leads to increased expression of GIRK channels147, which may serve as a possible neuroprotection for inappropriate activity. In support of this idea, stimulation of galanin type 2 receptors that activate GIRK channels prevents kindled epileptogenesis in rats148, highlighting GIRK channels as a novel target for anticonvulsants.
