ADENOSINE A(1) ANTAGONISM INCREASES SPECIFIC SYNAPTIC FORMS OF GLUTAMATE RELEASE DURING ANOXIA, REVEALING A UNIQUE SOURCE OF EXCITATION

The role of the adenosine A(1) receptor in the modulation of anoxia-in duced synaptic glutamate release was examined in CA1 pyramidal neurons by whole-cell voltage-clamp recording in the rat hippocampal slice pr eparation. Anoxia leads to an increased action potential-independent s ynaptic glutamate release in the form of a higher frequency of miniatu re excitatory postsynaptic currents (mEPSCs). This increase is not sig nificantly affected when slices are preincubated in the adenosine Al r eceptor antagonist, 8-cyclopentyl-1, 3-dipropylxanthine (DPCPX). A sec ond population of spontaneous inward currents, however, occurs in DPCP X-treated slices during a well-defined period following the onset of a noxia. Their suppression by glutamate antagonists, tetrodotoxin, or by the cutting of the Schaffer collateral pathway indicates that they re present action potential-dependent, glutamatergic excitatory postsynap tic currents (ap-EPSCs) originating from CA3 pyramidal neurons. CA3 ne urons were examined in current-clamp whole-cell patch mode to determin e the origin of this increased orthodromic excitation. After the onset of anoxia, CA3 cells initially exhibit a small depolarization or hype rpolarization associated with a decrease in input resistance. This is followed by transient depolarization (the depolarizing ''nub''), which is associated with an increase in input resistance. The nub evoked si ngle as well as bursts of action potentials in CA3 neurons. The occurr ence of these CA3 nub-elicited action potentials coincides with that o f ap-EPSCs recorded in the CA1 cells. Recording with cesium- rather th an standard potassium-containing electrodes results in the suppression of the nub and its associated increase in input resistance. In conclu sion we have shown that adenosine tone plays an important role in supp ressing anoxia-induced spontaneous ap-EPSCs but not action potential-i ndependent mEPSCs in CA1 neurons. These EPSCs originate from a depolar ization in CA3 pyramidal neurons, which is associated with an increase in resistance. This previously undescribed phenomenon likely results from a decrease in the conductance of an unidentified potassium channe l. (C) 1996 Wiley-Liss, Inc.