Kir3.3 is a member of the Kir3.x subfamily that includes four members (Kir3.1- Kir3.4). The Kir3 family is characterized by the fact that the channels can be activated by neurotransmitters and other factors acting via the activation of G-protein coupled receptors. Binding of the corresponding ligand to the G-protein receptor induces the dissociation of Ga-GTP from the Gbg dimer. The latter directly binds to Kir3 and activates the channel.n Kir3.3 is mainly expressed in the brain, were it co-assembles with Kir3.1 or Kir3.2. The functional impact of Kir3.3 is less well understood than the other Kir3 channels. However, heteromers composed of Kir3.2 and Kir3.3 were found to be primarily responsible for the opioid-induced current and hyperpolarization observed in mouse locus ceruleus (LC) neurons