Adenosine A1 receptors presynaptically modulate excitatory synaptic input onto subiculum neurons.
Adenosine is an endogenous neuromodulator previously shown to suppress synaptic transmission and membrane excitability in the CNS. In this study we have determined the actions of adenosine on excitatory synaptic transmission in the subiculum, the main output area for the hippocampus. Adenosine (10 microM) reversibly inhibited excitatory post synaptic currents (EPSCs) recorded from subiculum neurons. These actions were mimicked by the A(1) receptor-specific agonist, N(6)-cyclopentyl-adenosine (CPA, 10 nM) and blocked by the A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 500 nM), but were unaffected by the A(2A) antagonist ZM 241385 (50 nM). In membrane excitability experiments, bath application of adenosine and CPA reversibly inhibited action potentials (AP) in subiculum neurons that were evoked by stimulation of the pyramidal cell layer of the CA1, but not by depolarizing current injection steps in subiculum neurons, suggesting a presynaptic mechanism of action. In support, adenosine and CPA application reduced mEPSC frequency without modulating mEPSC amplitude. These studies suggest that modulation of subiculum neuron excitability by adenosine is mediated via presynaptic A(1) receptors.
Hargus
Nicholas J
NJ
Department of Anesthesiology, University of Virginia, Charlottesville, VA 22908, USA.
Bertram
Edward H
EH
Patel
Manoj K
MK
D000200:Action Potentials / Q000187:drug effects; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002491:Central Nervous System Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D002491:Central Nervous System Agents; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D014227:Triazines; D014230:Triazoles; D014970:Xanthines; C097270:ZM 241385; C048599:N(6)-cyclopentyladenosine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine