Endogenous activation of adenosine A1 receptors, but not P2X receptors, during high-frequency synaptic transmission at the calyx of Held.
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 ATPgammaS (100 microM) was mimicked by adenosine application and was blocked by DPCPX (10 microM), 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 degrees 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.
Department of Cell Physiology and Pharmacology, University of Leicester, United Kingdom.
Adrian Y C
AY
Wong
Brian
B
Billups
Jamie
J
Johnston
Richard J
RJ
Evans
Ian D
ID
Forsythe
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000241:Adenosine / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001306:Auditory Pathways / Q000187:drug effects / Q000502:physiology*; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D051381:Rats; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058469:Receptors, Purinergic P2X; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D058907:Adenosine A1 Receptor Agonists; D058910:Purinergic P2 Receptor Agonists; D043682:Receptor, Adenosine A1; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D000255:Adenosine Triphosphate; D000241:Adenosine