Present address: Department of Pharmacology, University College London, Gower street, London WC1E 6BT, UK.
Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neurons
Version of Record online: 20 DEC 2001
European Journal of Neuroscience
Volume 13, Issue 12, pages 2195–2204, June 2001
How to Cite
Chesnoy-Marchais, D. and Cathala, L. (2001), Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neurons. European Journal of Neuroscience, 13: 2195–2204. doi: 10.1046/j.0953-816x.2001.01599.x
- Issue online: 20 DEC 2001
- Version of Record online: 20 DEC 2001
- Received 19 February 2001, revised 3 April 2001, accepted 19 April 2001
- GABAA receptor;
- glycine receptor;
- l-type calcium channel;
Although glycine receptors (GlyRs) are responsible for the main spinal inhibitory responses in adult vertebrates, in the embryo they have been reported to mediate depolarizing responses, which can sometimes activate dihydropyridine-sensitive l-type calcium channels. However, these channels are not the only targets of dihydropyridines (DHPs), and we questioned whether GlyRs might be directly modulated by DHPs. By whole-cell recording of cultured spinal neurons, we investigated modulation of glycine responses by the calcium channel antagonists, nifedipine, nitrendipine, nicardipine and (R)-Bay K 8644, and by the calcium channel, agonist (S)-Bay K 8644. At concentrations between 1 and 10 µm, all these DHPs could block glycine responses, even in the absence of extracellular Ca2+. The block was stronger at higher glycine concentrations, and increased with time during each glycine application. Nicardipine blocked GABAA responses from the same neurons in a similar manner. In addition to their blocking effects, nitrendipine and nicardipine potentiated the peak responses to low glycine concentrations. Both effects of extracellular nitrendipine on glycine responses persisted when the drug was present in the intracellular solution. Thus, these modulations are related neither to calcium channel modulation nor to possible intracellular effects of DHPs. Another type of calcium antagonist, verapamil (10–50 µm), also blocked glycine responses. Our results suggest that some of the effects of calcium antagonists, including the neuroprotective and anticonvulsant effects of DHPs, might result partly from their interactions with ligand-gated chloride channels.