Would calcium or potassium channels be responsible for cardiac arrest produced by adenosine and ATP in the right atria of Wistar rats?

Abstract

Autonomic nerves release ATP, which is processed into adenosine in the synaptic cleft. Adenosine and ATP exert a negative chronotropic effect in the heart. This study aims to evaluate adenosine and P2 receptors and cellular signalling in cardiac arrest produced by purines in the heart. Right atria of adult Wistar rats were used to evaluate the effects of adenosine, ATP and CPA (an adenosine A1 receptor agonist), in the presence and absence of DPCPX, an adenosine A1 receptor antagonist. Effects of adenosine A2 and A3 receptors agonists and antagonists were also investigated. Finally, involvement of calcium and potassium channels in these responses was assessed using BayK 8644 and 4-Aminopyridine. Cumulative concentration-effect curves of adenosine and CPA resulted in a negative chronotropic effect culminating in cardiac arrest at 1000μM (adenosine) and 1µM (CPA). Furthermore, ATP produced a negative chronotropic effect at 1-300µM and cardiac arrest at 1000μM in the right atrium. ATPγS (a non-hydrolysable analogue of ATP) reduced chronotropism only. The effects of adenosine, CPA and ATP were inhibited by DPCPX, a selective adenosine A1 receptor antagonist. The selective adenosine A2 and A3 receptors antagonists did not alter the chronotropic response of adenosine. 4-Aminopyridine, a blocker of potassium channels at 10mM, prevented the cardiac arrest produced by adenosine and ATP, while BayK 8644, activator of calcium channels, did not prevent cardiac arrest. Adenosine A1 receptor activation by adenosine and ATP produces cardiac arrest in the right atrium of Wistar rats predominantly through activation of potassium channels.

• Authors: Henrique Camara, Juliano Quintella Dantas Rodrigues, Gabriel Andrade Alves, Edilson Dantas da Silva Junior, Afonso Caricati-Neto, Antônio G Garcia, Aron Jurkiewicz
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 768 Pg. 199-206 (Dec 05 2015) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 26528795 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Calcium Channels
• Potassium Channels
• Purinergic P1 Receptor Agonists
• Receptors, Purinergic P1
• Adenosine Triphosphate
• Adenosine

Topics

• Adenosine (pharmacology)
• Adenosine Triphosphate (pharmacology)
• Animals
• Calcium Channels (metabolism)
• Dose-Response Relationship, Drug
• Heart Arrest (chemically induced, metabolism, pathology, physiopathology)
• Heart Atria (drug effects, metabolism, pathology, physiopathology)
• Heart Rate (drug effects)
• Male
• Potassium Channels (metabolism)
• Purinergic P1 Receptor Agonists (pharmacology)
• Rats
• Rats, Wistar
• Receptors, Purinergic P1 (metabolism)