GIRK channels are implicated in the pathophysiology of several diseases, including epilepsy, addiction, Down’s syndrome, ataxia and Parkinson’s disease. Two broad principles have been distinguished. First, loss of GIRK function can lead to excessive excitability leading, such as in epilepsy, while a gain of GIRK function can significantly reduce neural activity, as postulated in Down’s syndrome. Second, loss of selectivity can cause ion fluxes across GIRK channels, such as excessive K+ efflux that triggers cell death, exemplified in a model of Parkinson’s disease.
