High-threshold Ca2+ currents in rat hippocampal interneurones and their selective inhibition by activation of GABAB receptors

Nevin A. Lambert, Wilkie A. Wilson

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)115-127
Number of pages13
JournalJournal of Physiology
Volume492
Issue number1
DOIs
StatePublished - Apr 1 1996

ASJC Scopus subject areas

  • Physiology

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