Adenosine A1 Receptors Mediate Presynaptic Inhibition of Retinotectal Synaptic Transmission: Uncoupling by C-Kinase Activation and Role in LTP During Regeneration. Chunyi Zhang and John T. Schmidt. Dept. of Biological Sciences and Neurobiology Research Center, University at Albany, SUNY. 1400 Washington Ave., Albany, NY 12222.
APStracts 4:306N, 1997.
ABSTRACT
Presynaptic adenosine receptors inhibit transmitter release at many synapses and are known to exist on retinotectal terminals (Braas et al. 1987 PNAS84: 3906). In this paper we show that adenosine decreases retinotectal field potentials by about 30% and investigate the mechanism. First, as judged by the effects of specific calcium channel blockers, retinotectal transmission was mediated almost exclusively by N-type calcium channels which are known to be modulated by adenosine A1 receptors. Transmission was completely blocked by either w-Conotoxin GVIA (-100%, N-type blocker) or w-Conotoxin MVIIC (-99%, N, P and Q-type blocker), and was not significantly affected by w-Agatoxin IVA (+1.7%ñ9.3%, P,Q-type blocker), but was augmented slightly by nifedipine (+9.3ñ2.1%, L-type blocker). Second, the adenosine inhibition was presynaptic, as indicated by a 43% increase in paired-pulse facilitation. Third, the selective A1 agonist cyclohexyl adenosine (CHA) at 50 nM caused a 21% decrease in amplitude, while the selective A2 agonist DPMA at 100 nM caused a 24% increase. Fourth, the selective A1 antagonist DPCPX alone produced an increase in the field potential, suggesting a tonic inhibition mediated by endogenous adenosine. Fifth, pertussis toxin eliminated adenosine inhibition implicating Gi or Go protein coupling. Sixth, C-kinase activation eliminated the A1- mediated inhibition. In regenerating projections, adenosine also caused a decrease in transmission (-30ñ12%), but after induction of LTP via trains of stimuli or via treatment with the phosphatase inhibitor okadaic acid, the adenosine response was converted to an augmentation. Since LTP is associated with C-kinase activation, this is consistent with C-kinase uncoupling the A1 receptor from inhibiting N-type Ca2+ channels. This uncovers the A2-mediated augmentation as demonstrated in normals with DPMA. Such an effect could account in part for the LTP of immature synapses and the change from rapidly fatiguing to robust synaptic transmission. 

Received 25 August 1997; accepted in final form 24 October 1997.
APS Manuscript Number J705-7.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997