1. Whole-cell calcium currents were recorded from visually identified inhibitory interneurones located in stratum radiatum (near the border with stratum lacunosum-moleculare) of area CA1 in rat hippocampal slices. Current-voltage (I-V) relationships in relatively well-clamped neurones showed that inward current activated between -50 and -40 mV (holding potential, -80 mV) and was maximal near -10 mV. Currents showed little inactivation over the course of 85 ms steps, and were completely blocked by removal of Ca2+ or addition of Cd2+. Prominent low-threshold currents were not observed under these conditions. 2. The calcium channels contributing to whole-cell currents in interneurones were examined using selective channel antagonists. The selective N-type calcium channel blocker ω-conotoxin GVIA (ω-CgTX-GVIA; 10 μM) irreversibly blocked 23·2 ± 2·8% of whole-cell currents. The P/Q-type antagonist ω-agatoxin IVA (ω-Aga-IVA; 1-5 μM) blocked 10·4 ± 3·3% of whole-cell currents. Block by ω-Aga-IVA was highly variable, ranging from 0 to 30%. The less selective conotoxin, ω-conotoxin MVIIC (ω-CTX-MVIIC; 5 μM) blocked 31·0 ± 2·7% of whole-cell currents. The selective L-type channel antagonist nifedipine (20 μM) blocked 27·5 ± 3·5% of whole-cell currents. 3. Whole-cell calcium currents were reversibly inhibited by the selective GABAB receptor agonists (±)-baclofen or CGP 27492 (1-3 μM; 18·9 ± 1·4%). This inhibition was reversed or prevented by the selective GABAB receptor antagonist CGP 55845A (1 μM). Inhibition of inward current activated by voltage ramps was voltage dependent, being greatest near -10 mV, and less pronounced at more positive or negative potentials. Inhibition of calcium currents by GABAB receptor agonists was accompanied by an apparent change in the kinetics of whole-cell currents consistent with a slowing of the rate of activation. CGP 27492 depressed calcium currents by 16·1 ± 1·9% before application of ω-CgTX-GVIA, and by 3·9 ± 2·0% after application of ω-CgTX-GVIA in the same cells (P < 0·005), consistent with preferential block of N-type calcium channels. 4. Neither adenosine (200 μM) nor the selective μ-opioid receptor agonist Tyr-D-Ala-Gly-MePhe-Gly-ol (DAMGO; 2 μM) inhibited calcium currents. Similarly, CGP 27492, but not adenosine or DAMGO, induced an outward current (at -70 mV) consistent with activation of inwardly rectifying potassium channels. 5. These results indicate that hippocampal inhibitory neurones located in stratum radiatum possess multiple calcium channel subtypes, including N-type, L-type, and at least two other types of high-threshold channels. Activation of GABAB receptors (but not adenosine or μ-opioid receptors) preferentially inhibits N-type channels in these neurones. Similar inhibition occurring in the terminals of interneurones could contribute to depression of inhibitory synaptic transmission by activation of GABAB autoreceptors.
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