Since KCNJ6/GIRK2 is related to alcohol action and addiction, it is possible that the finding has some relevance to alcoholism, although further studies linking KCNJ6 and human alcoholism are needed. As the KCNJ6 / GIRK2 system modulates neuronal excitability and inhibition at a cellular and network level (Signorini et al., 1997; Luscher and Slesinger, 2010) and/or epilepsy (Pei et al., 1999; Mazarati et al., 2006), it may be involved in the neuronal hyperexcitabity (CNS disinhibition) indexed by high resting EEG beta and low P3 amplitude, theta and delta EROs that we have observed in our studies of alcoholics and those at risk, including during reward processing (for reviews, see Porjesz et al., 2005; Rangaswamy and Porjesz, 2014; Kamarajan and Porjesz, 2015). According to the ‘CNS disinhibition’ model of alcoholism proposed by Begleiter and Porjesz (1999), a heritable hyperexcitability of the CNS caused by homeostatic imbalance is involved in a genetic predisposition to develop alcoholism and related externalizing disorders. This model seems more relevant now than ever before, and the KCNJ6 system could very well be one of the factors involved
