ArticleThe Journal of physiology2007
Ca2+-stimulated adenylyl cyclase isoform AC1 is preferentially expressed in guinea-pig sino-atrial node cells and modulates the I(f) pacemaker current.
Article in The Journal of physiology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 120 citations in OpenAlex.
- Intracellular CaInternational journal of molecular sciences · 2026Article
- cAMP-Activated EPAC Signaling Is an Integral Component of Cardiac Pacemaker Cell Automaticity.Circulation. Arrhythmia and electrophysiology · 2026Article
- Cardiac Pacemaker Cells Harness Stochastic Resonance to Ensure Fail-Safe Operation at Low Rates Bordering on Sinus Arrest.bioRxiv : the preprint server for biology · 2026Article
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- CaCells · 2024Review
- Activation of IPAmerican journal of physiology. Heart and circulatory physiology · 2024Article
- Pacemaker Channels and the Chronotropic Response in Health and Disease.Circulation research · 2024Review
- Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles.Frontiers in pharmacology · 2024Review
- CaCells · 2023Article
- Compartmentalized cAMP signalling and control of cardiac rhythm.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Timing mechanisms to control heart rhythm and initiate arrhythmias: roles for intracellular organelles, signalling pathways and subsarcolemmal CaPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- POPDC1 scaffolds a complex of adenylyl cyclase 9 and the potassium channel TREK-1 in heart.EMBO reports · 2022Article
- Adenylyl cyclase isoform 1 contributes to sinoatrial node automaticity via functional microdomains.JCI insight · 2022Article
- Preferential Expression of CaBiomolecules · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Functional Heterogeneity of Cell Populations Increases Robustness of Pacemaker Function in a Numerical Model of the Sinoatrial Node Tissue.Frontiers in physiology · 2022Article
- Inhibition of adenylyl cyclase 1 by ST034307 inhibits IPFrontiers in pharmacology · 2022Article
- The Role of POPDC Proteins in Cardiac Pacemaking and Conduction.Journal of cardiovascular development and disease · 2021Review
- Autonomic modulation of sinoatrial node: Role of pacemaker current and calcium sensitive adenylyl cyclase isoforms.Progress in biophysics and molecular biology · 2021Review
- What keeps us ticking? Sinoatrial node mechano-sensitivity: the grandfather clock of cardiac rhythm.Biophysical reviews · 2021Review
16 more citing papers are in PubMed but not listed here.
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6 authors.
Funding
Abstract
Ca(2+)-stimulated adenylyl cyclases (AC) are known to play important roles in neurons but have not previously been reported in the heart. Here we present the first evidence for selective expression of Ca(2+)-stimulated AC in the sino-atrial node (SAN) but not in ventricular muscle of the guinea-pig heart. The AC1 isoform of Ca(2+)-stimulated AC was shown to be present in SAN, both as mRNA using RT-PCR and as protein using immuno-blotting with a specific antibody. Confocal immuno-fluorescence studies detected membrane localization of AC1 in SAN cells, but no AC1 in ventricular muscle. Ca(2+)-stimulated AC8 may also be present in SAN. The functional importance of AC activity was investigated by monitoring activation of I(f) (gated by hyperpolarization and regulated by cAMP, which shifts activation to more depolarized voltages). Basal activity of AC in isolated SAN myocytes was demonstrated by the observations that an inhibitor of AC activity (MDL 12330A, 10 microm) shifted activation in the hyperpolarizing direction, while inhibition of phosphodiesterases (IBMX, 100 microm) shifted I(f) activation in the depolarizing direction. Buffering cytosolic Ca(2+) with the Ca(2+) chelator BAPTA (by exposure to BAPTA-AM) shifted activation of I(f) in the hyperpolarizing direction, and under these conditions the AC inhibitor MDL had little or no further effect. The actions of BAPTA were overcome by exposure to forskolin (10 microm), a direct stimulator of all AC isoforms, to restore cAMP levels. These effects are consistent with the functional importance of Ca(2+)-stimulated AC, which is expected to be fundamental to initiation and regulation of the heartbeat.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.