Physiology and pharmacology of native glycine receptors in developing rat ventral tegmental area neurons

Properties of whole-cell glycine-activated currents (I-Gly) of neurons freshly isolated from ventral tegmental area of rats between postnatal day (P) 0 and 40 (P0-P40) were examined using the gramicidin-perforated patch technique. I-Gly was present throughout the period of investigation and displayed age-related alternations in its kinetics, reversal potentials (E-Gly) and sensitivity to antagonists. During development, the time constant for desensitization of I-Gly decreased about two-fold, and the E-Gly shifted to more negative potentials. Specifically, E-Gly was -29 mV in neonatal (P0-P7) and decreased to -50 mV in adult (P24-P40) neurons. While the neonatal glycine receptors (GlyRs) are resistant to strychnine, the adult GlyRs are sensitive to STR. The values for 50% inhibition (IC50) of I-Gly was 110 and 12 nM in P0-P3 and P24-P40 neurons, respectively. Picrotoxin, on the other hand, was more effective in blocking neonatal neurons. The IC50 values were 17 and 231 mu M for the neonatal and adult neurons, respectively. These observations are discussed in terms of developmental changes of subunit composition of GlyRs and of intracellular Cl- concentrations. (C) 2000 Elsevier Science B.V. All rights reserved.