Modulation of glycine responses by dihydropyridines and verapamil in rat spinal neurons

Although glycine receptors (GlyRs) are responsible for the main spinal inhi bitory responses in adult vertebrates, in the embryo they have been reporte d to mediate depolarizing responses, which can sometimes activate dihydropy ridine-sensitive L-type calcium channels. However, these channels are not t he only targets of dihydropyridines (DHPs), and we questioned whether GlyRs might be directly modulated by DHPs. By whole-cell recording of cultured s pinal neurons, we investigated modulation of glycine responses by the calci um channel antagonists, nifedipine, nitrendipine, nicardipine and (R)-Bay K 8644, and by the calcium channel, agonist (S)-Bay K 3644. At concentration s between 1 and 10 mum, all these DHPs could block glycine responses, even in the absence of extracellular Ca2+. The block was stronger at higher glyc ine concentrations, and increased with time during each glycine application . Nicardipine blocked GABA(A) 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 rel ated neither to calcium channel modulation nor to possible intracellular ef fects of DHPs. Another type of calcium antagonist, verapamil (10-50 mum), a lso blocked glycine responses. Our results suggest that some of the effects of calcium antagonists, including the neuroprotective and anticonvulsant e ffects of DHPs, might result partly from their interactions with ligand-gat ed chloride channels.