title: The actions of adenosine 5'-triphosphate on guinea-pig intracardiac neurones in culture.
abstract: 1. The actions of adenosine 5'-triphosphate (ATP) and related nucleotides and nucleosides on the membrane ion conductances of M and AH type intracardiac neurones cultured from ganglia within the atria and interatrial septum of newborn guinea-pig heart were studied with intracellular current- and voltage-clamp techniques. 2. Approximately 74% (120 out of 161) of AH type cells and 41% (5 out of 12) M cells responded to direct application of ATP (500 microM) onto their soma. 3. In 41% of M and 43% of AH type cells, focal application of ATP (500 microM) evoked rapid depolarization with an increase in conductance which frequently elicited action potential discharge. The underlying inward current had a null potential of -11.2 mV and was reduced in solutions containing low extracellular sodium and calcium but unaffected by reduced chloride-containing solutions. 4. In a further 31% of AH type cells, ATP evoked a multi-component response consisting of an initial depolarization followed by a hyperpolarization and a slow prolonged depolarization. The current underlying the initial depolarization resulted from an increase in conductance and had a null potential of -19.1 mV. The current was increased in low chloride-containing solutions and was only slightly reduced in low sodium- and calcium-containing solutions. The subsequent hyperpolarization and outward current resulted from an increase in membrane conductance and had a null potential of -88.5 mV, which was close to the potassium equilibrium potential in these cells. The slow depolarization and inward current was not associated with change in membrane conductance. 5. In less than 2% of AH cells, ATP evoked a second type of slow depolarization. This was associated with a fall in conductance and had a null potential of -90.7 mV. 6. In 40% of AH cells, adenosine (10-100 microM) inhibited the calcium-sensitive potassium current responsible for the after-hyperpolarization. The action of adenosine was antagonized by the P1-purinoceptor antagonist 8-phenyltheophylline (1-10 microM). 7. The potency order of agonists for all of the ATP-evoked responses, except the slow depolarization associated with a fall in conductance was ATP > ADP with AMP and adenosine being ineffective. 8. Responses to ATP were only weakly desensitized by alpha,,Beta-methylene ATP (3 x 10-6 M) and the potency order of analogues was 2-methylthio ATP > ATP > alpha,beta-methylene ATP, indicating the involvement of receptors similar to P2Y purinoceptors.
authors.affiliation: Department of Anatomy and Developmental Biology, University College London.
authors.forename: T G
authors.initials: TG
authors.lastname: Allen
authors.forename: G
authors.initials: G
authors.lastname: Burnstock
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D002478:Cells, Cultured; D004566:Electrodes; D006168:Guinea Pigs; D006321:Heart / Q000294:innervation*; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009711:Nucleotides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects
chemical_list: D009711:Nucleotides; D015221:Potassium Channels; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate