Heart rate is slowed in part by acetylcholine-dependent activation of a cardiac potassium (K+) channel, I-KACh. Activated muscarinic receptors stimulate I-KACh via the G-protein beta gamma-subunits. It has been assumed that the inwardly rectifying K+-channel gene, GIRK1, alone encodes I-KACh. It is now shown that I-KACh is a heteromultimer of two distinct inwardly rectifying K+-channel subunits, GIRK1 and a newly cloned member of the family, CIR.