Among opioid-related genes, GIRK channels are attractive targets for the investigation of the relationship between genetic variations and sensitivity to opioid analgesics because they play a key role in opioid-induced analgesia [3]. Additionally, recent quantitative trait locus analysis and computational mapping have identified Kcnj9 (mouse Girk3) as a candidate gene affecting variability in the analgesia induced by multiple drug classes [4]. GIRK channels are members of the inwardly rectifying potassium channel family, and four subtypes (GIRK1-GIRK4) have been identified in mammals [5]. GIRK channels are expressed in many tissues, including the heart [6], spinal cord [7], [8], and various regions in the brain with different subunit compositions [9]–[11]. GIRK channel activation is triggered by activation of several Gi/o protein-coupled receptors, including opioid receptors [12]. Several studies using knockout mice have shown that opioid-induced GIRK channel activation co-expressed with opioid receptors leads to inhibition of nociceptive transmission and thus opioid-induced analgesia [6], [7], [13]–[15].
