Related Experiment Video

Updated: Aug 28, 2025

Methods for the Isolation, Culture, and Functional Characterization of Sinoatrial Node Myocytes from Adult Mice
09:32

Methods for the Isolation, Culture, and Functional Characterization of Sinoatrial Node Myocytes from Adult Mice

Published on: October 23, 2016

13.7K

Inhibition of adenylyl cyclase 1 by ST034307 inhibits IP3-evoked changes in sino-atrial node beat rate

Samuel J Bose1, Matthew J Read1, Emily Akerman1

  • 1Department of Pharmacology, University of Oxford, Oxford, United Kingdom.

Frontiers in Pharmacology
|September 15, 2022
PubMed

Insights

Adenylate cyclase 1 (AC1) plays a key role in atrial pacemaker activity regulation. Inhibiting AC1 with ST034307 reduced atrial tissue response to phenylephrine, demonstrating its involvement in alpha-adrenoreceptor stimulation.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Pharmacology

Background:

  • Atrial arrhythmias, including atrial fibrillation (AF), pose significant mortality and stroke risks.
  • The inositol trisphosphate (IP3) signaling pathway is a potential atrial-specific target for AF therapy.
  • Atrial IP3 signaling is linked to calcium-sensitive adenylyl cyclases AC1 and AC8.

Purpose of the Study:

  • To investigate the role of AC1 in atrial tissue and sino-atrial node (SAN) cell responses to phenylephrine (PE).
  • To determine if AC1 inhibition affects atrial and SAN cell function under adrenergic stimulation.

Main Methods:

  • Used the selective AC1 inhibitor ST034307 on intact mouse atrial tissue and isolated guinea pig atrial and SAN cells.
  • Measured changes in beating rate and contractile tension in atrial tissue.
  • Recorded calcium transients (CaT) in isolated atrial and SAN cells using Fluo-5F-AM.

Main Results:

  • ST034307 significantly reduced the maximum rate change in spontaneously beating mouse right atrial tissue exposed to PE (14.5% to 8.2%).
  • ST034307 did not inhibit the increase in tension in paced left atrial tissue.
  • ST034307 significantly reduced the beating rate of guinea pig SAN cells but did not affect PE-induced CaT amplitude changes in atrial cells.

Conclusions:

  • AC1 is pharmacologically involved in the downstream response of atrial pacemaker activity to alpha-adrenoreceptor stimulation.
  • AC1 inhibition impacts atrial rate but not contractility in response to adrenergic stimulation.
  • These findings highlight AC1 as a potential therapeutic target for atrial arrhythmias.

Keywords:
adenylyl cyclasecalcium signallingcardiac atriacyclic AMPinositol trisphosphatepacemakingsinoatrial node

More Related Videos

Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates07:42

Contractions of Human-iPSC-derived Cardiomyocyte Syncytia Measured with a Ca-sensitive Fluorescent Dye in Temperature-controlled 384-well Plates

Published on: October 18, 2018

6.3K
Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice09:20

Microelectrode Array Recording of Sinoatrial Node Firing Rate to Identify Intrinsic Cardiac Pacemaking Defects in Mice

Published on: July 5, 2021

3.2K

Related Concept Videos

G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory...
4.8K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.8K
Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers01:12

Antiarrhythmic Drugs: Class III Agents as Potassium Channel Blockers

Class III antiarrhythmic drugs are a group of medications that can prolong action potentials in the heart. They achieve this by blocking potassium channels or enhancing inward currents from sodium channels. However, these drugs have a unique property of "reverse use-dependence," which is most pronounced at slower heart rates and can lead to torsades de pointes—a specific type of arrhythmia. However, it is essential to note that excessive QT interval prolongation—a measure of...
1.2K
Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers01:24

Antiarrhythmic Drugs: Class II Agents as β-Adrenergic Blockers

Adrenergic stimulation generally impacts cardiac rate and rhythm. Specifically, stimulation of the β-adrenoceptors triggers an increase in intracellular calcium ion influx and pacemaker currents, which may cause arrhythmias. Catecholamines like adrenaline also demonstrate β2-adrenoceptor-mediated hypokalemia, impacting cardiac action potential and disrupting the normal cardiac rhythm. Class II antiarrhythmic drugs are β-adrenoceptor antagonists or β-blockers, which...
827
Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers01:20

Antiarrhythmic Drugs: Class IV Agents as Calcium Channel Blockers

Class IV antiarrhythmic drugs, such as verapamil and diltiazem, block calcium channels. They primarily affect the heart, slowing the conduction in calcium-dependent tissues like the SA and AV nodes. These drugs manage reentrant supraventricular tachycardia (SVT) and reduce ventricular rate in atrial flutter/fibrillation.
Verapamil, a calcium channel blocker, inhibits calcium movement across myocardial cell membranes and vascular smooth muscle. This results in the dilation of coronary and...
963
Adrenergic Receptors: ɑ Subtype01:31

Adrenergic Receptors: ɑ Subtype

Adrenoceptors are classified into α and ꞵ classes based on their potencies to catecholamine agonists. α-adrenoceptors show the following order of catecholamine potency:
Adrenaline ≥ Noradrenaline >> Isoprenaline
α-adrenoceptors are further divided into α1 and α2-adrenoceptors.
α1-Adrenoceptors: These receptors are located postsynaptically on the effector organs and cause constriction of smooth muscle mediated by activation of phospholipase...
1.7K