Effect of carbamazepine on stimulus-evoked Ca2+ fluxes in rat hippocampal slices and its interaction with A1-adenosine receptors.

In rat hippocampal slices superfused with a medium lacking Mg2+ ions, CA1 neurons generated burst discharges which were sensitive to blockade by 2-amino-5-phosphonovaleric acid (APV) and antagonized by 20-50 microM carbamazepine (CBZ). Decreases of [Ca2+]o (delta Ca), evoked by repetitive synaptic activation, were reduced in the presence of CBZ by 20-50%, associated with a reduced membrane depolarization. CBZ also abolished an APV-sensitive increase of delta Ca in the synaptic area elicited by theophylline. CBZ inhibited binding of the A1-adenosine receptor antagonist, [3H]8-cyclopentyl-1,3-dipropylxanthine [( 3H]DPCPX), in a dose-dependent manner. The displacement curve was shifted to the left in the presence of guanine nucleotide, suggesting that CBZ acts as an antagonist at A1-receptors. It is concluded that CBZ exerts its electrophysiological actions in the hippocampus at a site beyond the ligand recognition moiety.