title: Diadenosine pentaphosphate affects electrical activity in guinea pig atrium via activation of potassium acetylcholine-dependent inward rectifier.
abstract: Diadenosine pentaphosphate (Ap5A) belongs to the family of diadenosine polyphosphates, endogenously produced compounds that affect vascular tone and cardiac performance when released from platelets. The previous findings indicate that Ap5A shortens action potentials (APs) in rat myocardium via activation of purine P2 receptors. The present study demonstrates alternative mechanism of Ap5A electrophysiological effects found in guinea pig myocardium. Ap5A (10-4M) shortens APs in guinea pig working atrial myocardium and slows down pacemaker activity in the sinoatrial node. P1 receptors antagonist DPCPX (10-7M) or selective GIRK channels blocker tertiapin (10-6M) completely abolished all Ap5A effects, while P2 blocker PPADS (10-4M) was ineffective. Patch-clamp experiments revealed potassium inward rectifier current activated by Ap5A in guinea pig atrial myocytes. The current was abolished by DPCPX or tertiapin and therefore was considered as potassium acetylcholine-dependent inward rectifier (IKACh). Thus, unlike rat, in guinea pig atrium Ap5A produces activation of P1 receptors and subsequent opening of KACh channels leading to negative effects on cardiac electrical activity.
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia. abram340@mail.ru.|Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia. abram340@mail.ru.
authors.forename: Denis V
authors.identifier: http://orcid.org/0000-0001-5751-8853
authors.initials: DV
authors.lastname: Abramochkin
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia.
authors.forename: Viktoria M
authors.initials: VM
authors.lastname: Karimova
authors.affiliation: Department of Human and Animal Physiology, Lomonosov Moscow State University, Leninskiye Gory, 1, 12, Moscow, Russia.
authors.forename: Tatiana S
authors.initials: TS
authors.lastname: Filatova
authors.affiliation: Department of Physiology, Pirogov Russian National Research Medical University, Moscow, Russia.
authors.forename: Andre
authors.initials: A
authors.lastname: Kamkin
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000200:Action Potentials; D000818:Animals; D016275:Atrial Function / Q000187:drug effects*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D011188:Potassium / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists* / Q000378:metabolism; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
chemical_list: D015226:Dinucleoside Phosphates; D024661:Potassium Channels, Inwardly Rectifying; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; D000109:Acetylcholine; D011188:Potassium
keywords: Action potential; Atrium; Diadenosine pentaphosphate; Guinea pig; Heart; I KACh; Ionic current; Purine receptors