The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 501-510
Copyright ©1998 The American Physiological Society

Adenosine A1 Receptors Mediate Retinotectal Presynaptic Inhibition: Uncoupling by C-Kinase and Role in LTP During Regeneration

Chunyi Zhang and John T. Schmidt

Department of Biological Sciences and Neurobiology Research Center, State University of New York, Albany, New York 12222

Zhang, Chunyi and John T. Schmidt. Adenosine A1 receptors mediate retinotectal presynaptic inhibition: uncoupling by C-kinase and role in LTP during regeneration. J. Neurophysiol. 79: 501-510, 1998. Presynaptic adenosine receptors inhibit transmitter release at many synapses and are known to exist on retinotectal terminals. In this paper we show that adenosine decreases retinotectal field potentials by ~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 -Conotoxin GVIA (100%, N-type blocker) or -Conotoxin MVIIC (99%, N-, P- and Q-type blocker) and was not significantly affected by -Agatoxin IVA [+1.7 ± 9.3% (SE), P-,Q-type blocker], but was augmented slightly by nifedipine(+9.3 ± 2.1%, 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 and the selective A2 agonist N⁶-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine (DPMA) at 100 nM caused a 24% increase. Fourth, the selective A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) alone produced an increase in the field potential, suggesting a tonic inhibition mediated by endogenous adenosine. Fifth, pertussis toxin eliminated adenosine inhibition implicating G_i or G_o protein coupling. Sixth, C-kinase activation eliminated the A1-mediated inhibition. In regenerating projections, adenosine also caused a decrease in transmission (30 ± 12%), but after induction of long-term potentiation (LTP) via trains of stimuli or via treatment with the phosphatase inhibitor okadaic acid, the adenosine response was converted to an augmentation. Because 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.

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