Two types of G protein-coupled receptors – the muscarinic acetylcholine receptors and the beta adrenergic receptors – are key regulators of heart rate. When these receptors are activated, G proteins inside the cell split into two subunits, Gα (pale blue ovals) and Gβγ (green/purple circles). The release of adrenaline, for example, results in the activation of beta adrenergic receptors (βARs; bottom) by adrenaline (red circle) to increase the heart rate. The activation of a muscarinic acetylcholine receptor (M2R; top) by acetylcholine (red star) leads to the activation of GIRK ion channels and a subsequent drop in heart rate. It has been unclear why the Gβγ subunits released by M2Rs could activate GIRK channels, whereas the same Gβγ subunits released by βARs could not. Touhara and MacKinnon suggest that the fast kinetics of interactions between G proteins containing Gαi/o subunits and M2Rs releases high enough concentrations of Gβγ subunits to activate the GIRK channels (top). The interactions between G proteins containing Gαs subunits and βARs, on the other hand, are slower and cannot produce enough Gβγ subunits before they diffuse away or rebind to the Gαs subunits (bottom).