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Inositol trisphosphate (IP 3 ) is a Ca 2+ -mobilizing second messenger shown to modulate atrial muscle contraction and is thought to contribute to atrial fibrillation. Cellular pathways underlying IP 3 actions in cardiac tissue remain poorly understood, and the work presented here addresses the question whether IP 3 -mediated Ca 2+ release from the sarcoplasmic reticulum is linked to adenylyl cyclase activity including Ca 2+ -stimulated adenylyl cyclases (AC1 and AC8) that are selectively expressed in atria and sinoatrial node (SAN). Immunocytochemistry in guinea pig atrial myocytes identified colocalization of type 2 IP 3 receptors with AC8, while AC1 was located in close vicinity. Intracellular photorelease of IP 3 by UV light significantly enhanced the amplitude of the Ca 2+ transient (CaT) evoked by electrical stimulation of atrial myocytes (31 ± 6% increase 60 s after photorelease, n = 16). The increase in CaT amplitude was abolished by inhibitors of adenylyl cyclases (MDL-12,330) or protein kinase A (H89), showing that cAMP signaling is required for this effect of photoreleased IP 3 . In mouse, spontaneously beating right atrial preparations, phenylephrine, an α-adrenoceptor agonist with effects that depend on IP 3 -mediated Ca 2+ release, increased the maximum beating rate by 14.7 ± 0.5%, n = 10. This effect was substantially reduced by 2.5 µmol/L 2-aminoethyl diphenylborinate and abolished by a low dose of MDL-12,330, observations which are again consistent with a functional interaction between IP 3 and cAMP signaling involving Ca 2+ stimulation of adenylyl cyclases in the SAN pacemaker. Understanding the interaction between IP 3 receptor pathways and Ca 2+ -stimulated adenylyl cyclases provides important insights concerning acute mechanisms for initiation of atrial arrhythmias. NEW & NOTEWORTHY This study provides evidence supporting the proposal that IP 3 signaling in cardiac atria and sinoatrial node involves stimulation of Ca 2+ -activated adenylyl cyclases (AC1 and AC8) by IP 3 -evoked Ca 2+ release from junctional sarcoplasmic reticulum. AC8 and IP 3 receptors are shown to be located close together, while AC1 is nearby. Greater understanding of these novel aspects of the IP 3 signal transduction mechanism is important for future study in atrial physiology and pathophysiology, particularly atrial fibrillation.