The actions of adenosine 5′‐triphosphate on guinea‐pig intracardiac neurones in culture

• Published in: British journal of pharmacology 1990-06, Vol.100 (2), p.269-276
• Main Authors: Allen, T.G.J., Burnstock, G.
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine Diphosphate - pharmacology; Adenosine Monophosphate - pharmacology; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Animals, Newborn - physiology; Biological and medical sciences; Cells, Cultured; Electrodes; Fundamental and applied biological sciences. Psychology; Guinea Pigs; Heart; Heart - innervation; Membrane Potentials - drug effects; Neurons - drug effects; Nucleotides - pharmacology; Potassium Channels - drug effects; Vertebrates: cardiovascular system
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb15794.x

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 μm) onto their soma. 3 In 41% of m and 43% of AH type cells, focal application of ATP (500 μm) 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 μ m) 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 μm). 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 α,β‐methylene ATP (3 × 10−6 m) and the potency order of analogues was 2‐methylthio ATP ≤ ATP > α,β‐methylene ATP, indicating the involvement of receptors similar to P2Y purinoceptors.