Chunk #79 — Potential for Translational Applications of Electrophysiological Measures of Brain Function — Electrophysiological Measures As Endophenotypes for Alcoholism
In a family-based genome-wide association study, Kang and colleagues (2012) used the same neurophysiological phenotype (frontal theta ERO in the visual oddball task) and found genome-wide significant association with several SNPs in KCNJ6, a gene that encodes the protein G-protein inward-rectifying potassium channel 2 (GIRK2). GIRK2 is widely distributed in the brain and is important in dopaminergic, cholinergic, GABAergic, and glutamatergic synapses (Saenz del Burgo et al. 2008). GIRK2-receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability and therefore is important in regulating excitability of neuronal networks. GIRK2 also is important in alcoholism studies, as it is directly activated by alcohol (Aryal et al. 2009; Blednov et al. 2001; Bodhinathan and Slesinger 2013; Hill et al. 2003; Kobayashi et al. 1999; Lewohl et al. 1999). In addition, GIRK2 receptors are important effectors in both opioid- and alcohol-induced pain relief (Ikeda et al. 2002) and are viable drug targets (Kobayashi et al. 2004; Lotsch and Geisslinger 2011).
