K_ir3.4 is a member of the G-protein regulated inward-rectifier K⁺ (GIRK) channel subfamily which is part of an inward-rectifier K⁺ channel superfamily. The GIRK subfamily comprises four members in mammals (K_ir3.1- K_ir3.4) that present the common topology of the inward-rectifier superfamily: two transmembrane domains flanking a highly conserved pore region with the N and C-terminus located intracellularly.

K_ir3.4 and the other K_ir3 family subunits can be activated by neurotransmitters and other factors via the activation of G-protein coupled receptors. Binding of the corresponding ligand to the G-protein receptor induces the dissociation of G α-GTP from the Gβγ dimer. The latter directly binds to K_ir3 and activates the channel. 

K_ir3.4 expression is largely confined to the heart, where it co-assembles with K_ir3.1 to form the prototypical muscarinic-gated K⁺ channel KACh. Indeed, knockout mice for K_ir3.4 showed impaired heart rate following vagal nerve stimulation.

A peptide toxin originating from the Apis mellifera bee venom, Tertiapin (#STT-250) was shown to be a potent blocker of K_ir3.4 containing channels (8.6 nM for the K_ir3.1/3.4 combination).⁴