PT - JOURNAL ARTICLE AU - Bose, Samuel J. AU - Read, Matthew AU - Capel, Rebecca A AU - Akerman, Emily AU - Ayagama, Thamali AU - Russell, Angela AU - Terrar, Derek A AU - Zaccolo, Manuela AU - Burton, Rebecca AB TI - Cross-talk between cAMP and Ca<sup>2+</sup> signalling in cardiac pacemaker cells involves IP<sub>3</sub>-evoked Ca<sup>2+</sup> release and stimulation of adenylyl cyclase 1 AID - 10.1101/2022.01.06.475211 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.01.06.475211 4099 - http://biorxiv.org/content/early/2022/01/06/2022.01.06.475211.short 4100 - http://biorxiv.org/content/early/2022/01/06/2022.01.06.475211.full AB - Atrial arrhythmias, such as atrial fibrillation (AF), are a major mortality risk and a leading cause of stroke. The IP3 signalling pathway has been proposed as an atrial specific target for AF therapy, and atrial IP3 signalling has been linked to the activation of calcium sensitive adenylyl cyclases AC1 and AC8. Here we investigated the involvement of AC1 in the response of intact mouse atrial tissue and isolated guinea pig atrial and sinoatrial node (SAN) cells to the α-adrenoceptor agonist phenylephrine (PE) using the selective AC1 inhibitor ST034307. The maximum rate change of spontaneously beating mouse right atrial tissue exposed to PE was reduced from 14.46 % to 8.17% (P = 0.005) in the presence of 1 μM ST034307, whereas the increase in tension generated in paced left atrial tissue in the presence of PE was not inhibited by ST034307 (Control = 14.20 %, ST034307 = 16.32 %; P &gt; 0.05). Experiments were performed using isolated guinea pig atrial and SAN cells loaded with Fluo-5F-AM to record changes in calcium transient amplitude (CaT) generated by 10μM PE in the presence and absence of 1μM ST034307. ST034307 significantly reduced the beating rate of SAN cells (0.34-fold decrease; P = 0.004), but did not result in an inhibition of CaT amplitude increase in response to PE in atrial cells. The results presented here demonstrate the involvement of AC1 in the downstream response of atrial pacemaker activity to α-adrenoreceptor stimulation and IP3R calcium release.Competing Interest StatementThe authors have declared no competing interest.