HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fieber, L A Articles by Adams, D J Search for Related Content PubMed PubMed Citation Articles by Fieber, L A Articles by Adams, D J

Department of Molecular and Cellular Pharmacology, University of Miami, School of Medicine, FL 33101.

1. The excitatory response of cultured neurones of rat parasympathetic cardiac ganglia to extracellular adenosine 5'-triphosphate (ATP) was examined using the whole-cell isolated membrane patch recording configurations of the patch clamp technique. The short latency between ATP application and activation of the membrane current (less than 20 ms) suggests a direct coupling between purinergic receptor and ion channel. The response was maintained during exposure to ATP suggesting that receptor desensitization is not a factor in current decay. 2. The current-voltage (I-V) relationship for macroscopic ATP-evoked currents showed strong inward rectification in the presence and absence of external divalent cations and a reversal potential of +10 mV (NaCl outside, CsCl inside). Unitary ATP-activated currents in cell-attached membrane patches exhibited a linear (ohmic) I-V relationship with a slope conductance of approximately 60 pS. 3. The order of agonist potency for the purinergic receptor-mediated response was 2-methylthioATP = ATP greater than ADP greater than AMP greater than adenosine = alpha,beta-methylene ATP greater than beta,gamma-methylene ATP, a sequence consistent with a P2y receptor subtype. ATP-evoked currents were attenuated by alpha,beta-methylene ATP (IC50 approximately 10 microM) and reversibly inhibited in a dose-dependent manner by Reactive Blue 2 (Kd = 1 microM). 4. The amplitude of the ATP-evoked current was dependent on the extracellular Na+ concentration. The direction of the shift in reversal potential when NaCl was replaced with mannitol indicated that the purinergic receptor channel is cation selective. The cation permeability relative to Na+ followed the ionic selectivity sequence Ca2+ (1.48) greater than Na+ (1.0) greater than Cs+ (0.67). Anions were not measurably permeant. 5. ATP and ACh-evoked responses in rat intracardiac neurones are mediated by distinct receptor channels. The ATP-activated channels in cardiac neurones may contribute to non-cholinergic, non-adrenergic neurotransmission and mediate, in part, the vagal innervation of the mammalian heart.

This article has been cited by other articles:

				G. Burnstock Physiology and Pathophysiology of Purinergic Neurotransmission Physiol Rev, April 1, 2007; 87(2): 659 - 797. [Abstract] [Full Text] [PDF]

				R. A. North Molecular Physiology of P2X Receptors Physiol Rev, October 1, 2002; 82(4): 1013 - 1067. [Abstract] [Full Text] [PDF]

				K. Xiong, R. W. Peoples, J. P. Montgomery, Y. Chiang, R. R. Stewart, F. F. Weight, and C. Li Differential Modulation by Copper and Zinc of P2X2 and P2X4 Receptor Function J Neurophysiol, May 1, 1999; 81(5): 2088 - 2094. [Abstract] [Full Text] [PDF]

				V. Ralevic and G. Burnstock Receptors for Purines and Pyrimidines Pharmacol. Rev., September 1, 1998; 50(3): 413 - 492. [Abstract] [Full Text] [PDF]

				M. Rogers, L. M. Colquhoun, J. W. Patrick, and J. A. Dani Calcium Flux Through Predominantly Independent Purinergic ATP and Nicotinic Acetylcholine Receptors J Neurophysiol, March 1, 1997; 77(3): 1407 - 1417. [Abstract] [Full Text] [PDF]