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 (IC(50)) 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 IC(50) values were 17 and 231 microM 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.