This is further supported by a recent family GWAS study in COGA with a genomewide significant finding in another neurotransmitter-related gene – KCNJ6 (a potassium inward rectifier channel, GIRK2) and frontal theta EROs (Kang et al., 2012). These results suggest that KCNJ6 or its product GIRK2 may account for some of the variations in theta oscillations. GIRK2 receptor activation contributes to slow inhibitory postsynaptic potentials that modulate neuronal excitability, and therefore influence neuronal networks (Luscher and Slesinger, 2010). Animal models have shown that GIRK channels are directly activated by ethanol and are important effectors in both opioid- and ethanol-induced analgesia and are considered a viable drug target; GIRK2 also modulates opioid effects on analgesia and addiction in humans. Thus these findings between theta EROs and KCNJ6 have important implications for neural excitability and alcohol addiction.
