Presynaptic inhibition at excitatory hippocampal synapses: development and role of presynaptic Ca2+ channels.
1. Presynaptic inhibition of excitatory postsynaptic currents (EPSCs) induced by activation of adenosine receptors was examined at hippocampal synapses in cell culture. Changes in the degree of presynaptic inhibition during development were examined. The results were then used to test the role of presynaptic Ca2+ channels in presynaptic inhibition. 2. Application of the selective A1 adenosine receptor agonist N6-cyclopentyladenosine (CPA) reduced EPSCs measured with the use of whole cell voltage-clamp procedures. In cells grown in culture for < 15 days, CPA (100 nM) inhibited EPSCs by 74 +/- 2%. In cells grown in culture for > 20 days, the same concentration of CPA inhibited EPSCs by 47 +/- 3%. 3. In mature cells (grown in culture for > 20 days), application of the selective N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CTx GVIA; 2.5 microM) partially occluded the effects of CPA. In contrast, the P/Q channel blocker omega-Aga IVA enhanced the effects of CPA. Both toxins reduced the amplitude of the EPSC. 4. omega-CTx GVIA was applied to the EPSC that remained after application of 100 nM CPA. Under these conditions, omega-CTx GVIA reduced the EPSC by less than when omega-CTx GVIA was applied under control conditions. In contrast, when omega-Aga IVA was applied in the presence of CPA, the toxin reduced the EPSC to a greater extent than when it was applied under control conditions. 5. Somatic Ca(2+)-channel currents were inhibited by CPA. This effect was partially occluded by pretreatment with omega-CTx GVIA but was unaffected by pretreatment with omega-Aga IVA (1 microM). Both toxins blocked part of the somatic Ca(2+)-channel current. 6. The results indicate that inhibition of presynaptic N-type Ca2+ channels accounted for 40-50% of presynaptic inhibition, another type of Ca2+ channel may participate as well. In addition, the efficacy of presynaptic inhibition declined during synapse maturation due in part to a developmental decline in the relative contribution of N-type channels to transmitter release.
Scholz
K P
KP
Department of Pharmacological and Physiological Sciences, University of Chicago, Illinois 60637, USA.
Miller
R J
RJ
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine