Adenosine A(1)-receptor-mediated tonic inhibition of glutamate release at rat hippocampal CA3-CA1 synapses is primarily due to inhibition of N-type Ca(2+) channels

Eur J Pharmacol. 2004 Sep 24;499(3):265-74. doi: 10.1016/j.ejphar.2004.07.113.

Abstract

The voltage-gated Ca(2+) channels responsible for synaptic transmission at CA3-CA1 synapses are mainly P/Q- and N-types. It has been shown that tonic inhibition of transmission due to activation of adenosine A(1) receptors occurs at this synapse. We have recently developed a technique to monitor synaptically released glutamate which is based on synaptically induced glial depolarisation. Using this technique, we have examined the effects of different voltage-gated Ca(2+) channel blockers on glutamate release. Under conditions in which the adenosine A(1) receptor was not blocked, omega-AgaIVA (a P/Q-type voltage-gated Ca(2+) channel blocker) suppressed synaptically induced glial depolarisation to a greater extent than omega-CgTxGVIA (an N-type voltage-gated Ca(2+) channel blocker) did. In contrast, in the presence of an adenosine A(1) receptor antagonist, omega-AgaIVA was less effective at suppressing synaptically induced glial depolarisation than omega-CgTxGVIA. These results indicate that, in the absence of adenosine A(1) receptor-mediated tonic inhibition, the contribution of N-type is much greater than that of P-type, and that N-types are the primary target of tonic inhibition in normal conditions in which adenosine A(1) receptor-mediated tonic inhibition is present.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, N-Type / physiology*
  • Dose-Response Relationship, Drug
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Male
  • Rats
  • Rats, Wistar
  • Receptor, Adenosine A1 / physiology*
  • Synapses / drug effects
  • Synapses / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • Theophylline / analogs & derivatives*
  • Theophylline / pharmacology
  • omega-Agatoxin IVA / pharmacology
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Calcium Channel Blockers
  • Calcium Channels, N-Type
  • Receptor, Adenosine A1
  • omega-Agatoxin IVA
  • 8-cyclopentyl-1,3-dimethylxanthine
  • Glutamic Acid
  • N(6)-cyclopentyladenosine
  • omega-Conotoxin GVIA
  • Theophylline
  • Adenosine