Endogenous Activation of Adenosine A1 Receptors, but Not P2X Receptors, During High-Frequency Synaptic Transmission at the Calyx of Held

• Published in: Journal of neurophysiology 2006-06, Vol.95 (6), p.3336-3342
• Main Authors: Wong, Adrian Y. C, Billups, Brian, Johnston, Jamie, Evans, Richard J, Forsythe, Ian D
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Adenosine - pharmacology; Adenosine A1 Receptor Agonists; Adenosine Triphosphate - metabolism; Animals; Auditory Pathways - drug effects; Auditory Pathways - physiology; Brain Stem - drug effects; Brain Stem - physiology; Cells, Cultured; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Neurons - drug effects; Neurons - physiology; Purinergic P2 Receptor Agonists; Rats; Receptor, Adenosine A1 - metabolism; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.00694.2005

1 Department of Cell Physiology and Pharmacology and 2 Medical Research Council Toxicology Unit, University of Leicester, Leicester, United Kingdom Submitted 1 July 2005; accepted in final form 10 February 2006 Activation of presynaptic receptors plays an important role in modulation of transmission at many synapses, particularly during high-frequency trains of stimulation. Adenosine-triphosphate (ATP) is coreleased with several neurotransmitters and acts at presynaptic sites to reduce transmitter release; such presynaptic P2X receptors occur at inhibitory and excitatory terminals in the medial nucleus of the trapezoid body (MNTB). We have investigated the mechanism of purinergic modulation during high-frequency repetitive stimulation at the calyx of Held synapse. Suppression of calyceal excitatory postsynaptic currents (EPSCs) by ATP and ATP S (100 µM) was mimicked by adenosine application and was blocked by DPCPX (10 µM), indicating mediation by adenosine A1 receptors. DPCPX enhanced EPSC amplitudes during high-frequency synaptic stimulation, suggesting that adenosine has a physiological role in modulating transmission at the calyx. The Luciferin-Luciferase method was used to probe for endogenous ATP release (at 37°C), but no release was detected. Blockers of ectonucleotidases also had no effect on endogenous synaptic depression, suggesting that it is adenosine acting on A1 receptors, rather than degradation of released ATP, which accounts for presynaptic purinergic suppression of synaptic transmission during physiological stimulus trains at this glutamatergic synapse. Address for reprint requests and other correspondence: Professor Ian D. Forsythe, MRC Toxicology Unit, University of Leicester, Leicester, LE1 9HN. United Kingdom. (E-mail: IDF{at}le.ac.uk )