Glycine-activated chloride currents of neurons freshly isolated from the ventral tegmental area of rats

Properties of whole-cell glycine currents (I(Gly)) of ventral tegmental area (VTA) neurons from 3- to 7-day old Sprague-Dawley rats were investigated with the patch-clamp technique. Ninety-three percent of the 126 neurons examined produced I(Gly) in response to glycine. For 70% of these neurons, I(Gly) did not decay in response to a threshold concentration of glycine (1- 5 μM). At elevated glycine concentrations, I(Gly) consistently decayed from a peak to a steady state (SS). I(Gly) increased in amplitude sigmoidally as a function of the concentration of agonist with an EC₅₀ of 32 μM. Strychnine (STR), when co-applied with glycine after a prepulse of STR, suppressed both the peak and SS I(Gly) noncompetitively. In the absence of a prepulse, STR had a smaller effect on peak I(Gly) while increasing its decay rate; the SS amplitude decreased. These STR effects were concentration dependent with an IC₅₀ of 31 nM and 184 nM STR for the peak and SS I(Gly), with prepulse, respectively, and 732 nM and 193 nM for the peak and SS I(Gly), respectively, without prepulse. Picrotoxin (PTX) co-applied with glycine suppressed both the peak and the SS I(Gly) with an IC₅₀ of 25 μM. In contrast to STR, 1 min preincubation with PTX had no effect on I(Gly). Thus, PTX acts on the open channel. The inhibitory effects of both STR and PTX on I(Gly) did not depend on the membrane potential.