Glycine-activated chloride currents of neurons freshly isolated from the ventral tegmental area of rats.
Properties of whole-cell glycine currents (IGly) 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 IGly in response to glycine. For 70% of these neurons, IGly did not decay in response to a threshold concentration of glycine (1-5 microM). At elevated glycine concentrations, IGly consistently decayed from a peak to a steady state (SS). IGly increased in amplitude sigmoidally as a function of the concentration of agonist with an EC50 of 32 microM. Strychnine (STR), when co-applied with glycine after a prepulse of STR, suppressed both the peak and SS IGly noncompetitively. In the absence of a prepulse, STR had a smaller effect on peak IGly 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 IGly, with prepulse, respectively, and 732 nM and 193 nM for the peak and SS IGly, respectively, without prepulse. Picrotoxin (PTX) co-applied with glycine suppressed both the peak and the SS IGly with an IC50 of 25 microM. In contrast to STR, 1 min preincubation with PTX had no effect on IGly. Thus, PTX acts on the open channel. The inhibitory effects of both STR and PTX on IGly did not depend on the membrane potential.
Department of Anesthesiology, New Jersey Medical School (UMDNJ), Newark 07103-2714, USA. ye@umdnj.edu
J H
JH
Ye
J
J
Ren
P L
PL
Liu
J J
JJ
McArdle
D000818:Animals; D002469:Cell Separation; D018118:Chloride Channels / Q000187:drug effects* / Q000502:physiology; D004553:Electric Conductivity; D005998:Glycine / Q000494:pharmacology*; D018684:Glycine Agents / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology; D013681:Tegmentum Mesencephali / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D018118:Chloride Channels; D005998:Glycine; D018684:Glycine Agents; D010852:Picrotoxin; D013331:Strychnine