title: 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.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil.
authors.forename: Henrique
authors.initials: H
authors.lastname: Camara
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil. Electronic address: juliano.quintella@unifesp.br.
authors.forename: Juliano Quintella Dantas
authors.initials: JQ
authors.lastname: Rodrigues
authors.affiliation: Department of Biophysics, Federal University of São Paulo (UNIFESP), Brazil.
authors.forename: Gabriel Andrade
authors.initials: GA
authors.lastname: Alves
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil.
authors.forename: Edilson Dantas
authors.initials: ED
authors.lastname: da Silva Junior
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil.
authors.forename: Afonso
authors.initials: A
authors.lastname: Caricati-Neto
authors.affiliation: Instituto Teófilo Hernando, Universidad Autonoma de Madrid, Madrid, Spain.
authors.forename: Antônio G
authors.initials: AG
authors.lastname: Garcia
authors.affiliation: Department of Pharmacology, Federal University of São Paulo (UNIFESP), Brazil. Electronic address: aron.farm@epm.br.
authors.forename: Aron
authors.initials: A
authors.lastname: Jurkiewicz
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006323:Heart Arrest / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D015221:Potassium Channels / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018047:Receptors, Purinergic P1 / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D015221:Potassium Channels; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; D000255:Adenosine Triphosphate; D000241:Adenosine
keywords: 4-Aminopyridine (PubChem CID: 444229); ATPγS (PubChem CID: 440317); Adenosine receptors; BayK 8644 (PubChem CID: 2303); CGS21680 (PubChem CID: 3086599); Calcium channels; Cardiac arrest; DPCPX (PubChem CID: 1329); IB-MECA (PubChem CID: 123683); MRS 1220 (PubChem CID: 393595); MRS2179 (PubChem CID: 5311302); N(6)-Cyclopentyladenosine (PubChem CID: 657378); Potassium channels; Sinoatrial node; ZM 241385 (PubChem CID: 176407)