Figure 3. Either genetic ablation (top) or pharmacological targeting (bottom) of Girk4‐mediated I_KACh channels is able to prevent sick sinus syndrome and atrioventricular block in SANDD mimicking Ca_v1.3^−/− mice (Mesirca et al. 2016 ) .

Telemetric ECG recordings of Ca_v1.3^−/− mice show SAN bradycardia and 2nd degree atrioventricular block (top left). In contrast, Girk4^−/− mice present with normal SAN rate and no atrioventricular blocks (top centre). Crossing these mouse lines produces viable Ca_v1.3^−/−/Girk4^−/− animals with normal heart rate and rhythm (top right). When Ca_v1.3^−/− mice undergo an intraperitoneal injection of the GIRK pore blocker tertiapin‐Q (tertiapin, bottom centre) normalization of heart rate is observed (bottom right). The central panel shows a close up view of a structural model of tertiapin bound to the GIRK pore. K17 and D164 indicate residues important for tertiapin activity.