Brain Research, 416 (1987) 257-266 257 Elsevier BRE 12719 Differential effects of calcium entry blockers on pre- and postsynaptic influx of calcium in the rat hippocampus in vitro Roland S.G. Jones and Uwe H. Heinemann* Department of Neurophysiology, Max-Planck Institute for Psychiatry, Planegg-Martinsried (F.R. G. ) (Accepted 16 December 1986) Key words: Calcium entry blocker; CA1; Presynaptic calcium influx; Postsynaptic calcium influx A decrease in extracellular free Ca ([Ca2+]o) in response to stimulation of Schaffer collaterals could be recorded in or near the stra- tum pyramidale even when synaptic transmission was completely blocked. Under the same conditions, alvear stimulation also evoked a decrease in [Ca2+]oat the same site. We attributed the former to influx of Ca2+ into presynaptic terminals and the latter to influx into postsynaptic (pyramidal) cells. Both pre- and postsynaptic Ca 2+ influx were completely blocked by Ni 2+ (2.5 mM). Nifedipine (5-10 ~M), verapamil (50-100~M) and fendiline (100-200/~M) reduced the postsynaptic influx of Ca2+ but did not alter Ca2+ loss from the extracellular space into presynaptic terminals. The calcium channel activators, BAY-K 8644 and CGP 28,392, had no consistent effect on either pre- or postsynaptic influx. Occasional enhancement of both pre- and postsynaptic responses was seen. In most studies the agents were without effect and on occasions a reduction in both responses was seen. The results could indicate that Ca-channels at pre- and postsynaptic sites in CA 1may be of different types. INTRODUCTION In peripheral tissues, Ca entry blockers or 'antago- nists' such as verapamil and the dihydropyridines, e.g. nifedipine, nitrendipine etc,, are extremely ef- fective at inhibiting Ca influx via voltage-gated mem- brane channels 16. However, there is considerable doubt over the ability of these agents to block Ca channels in neuronal tissue. Electrophysioiogical studies have shown that Ca entry blockers reduce so- matic or axonal Ca conductance or Ca-dependent ac- tion potentials, but at much higher concentrations than those active in the periphery (see ref. 35 and Discussion in this paper). Neurochemical studies de- signed to look at presynaptic Ca influx indicate little effect of these drugs on uptake of radiolabelled Ca or on Ca-dependant transmitter release (see ref. 35). Recently, Louvel et al. 31 have reported a lack of effect of several Ca entry blockers on presynaptic in- flux of Ca into terminals of the Schaffer collaterals (SC) in CA~ of the rat hippocampus. These authors used the technique described by Heinemann et al. 22'28 to look at presynaptic Ca influx. Under condi- tions of blocked synaptic transmission, stimulation of presynaptic fibers results in measurable loss of Ca from the extracellular space. This loss is attributable to presynaptic uptake of Ca 22,28. Louvel et al. 31 found that most organic Ca entry blockers did not alter this decrease in [Ca2+]o . The same study also concluded that nifedipine could block postsynaptic Ca influx since it reduced synaptic potentials and the decline in [Ca2+]o elicited by SC stimulation when transmission was intact. We were interested in comparing the influence of Ca entry blockers on pre- and postsynaptic influx of Ca directly and simultaneously in the same experi- ment. Using the same technique described above we were able to record (presumed) presynaptic Ca up- take. At the same time, the CA t pyramidal cells were activated antidromically and the decrease in [Ca2+]o * Present address: Institut fur Physiologie, Universit~it K61n, Robert-Koch Strasse 39, D-5000 KOln 41, F.R.G. Correspondence: R.S.G. Jones, Present address: Department of Pharmacology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia. 0006-8993/87/$03.50 © 1987 Elsevier Science Publishers B.V. (Biomedical Division)