Binding sites, singly bound states, and conformation coupling shape GABA-evoked currents.
The time course of GABA-evoked currents is the main source of information on the GABA(A) receptor gating. Since the kinetics of these currents depends on the transitions between several receptor conformations, it is a major challenge to define the relations between current kinetics and the respective rate constants of the microscopic gating scheme. The aim of this study was to further explore the impact of different GABA(A) receptor conformations on the kinetics of currents elicited by ultra-fast GABA applications. We show that the rising phase and amplitude of GABA-evoked currents depend on desensitization and singly bound states. The occupancy of bound receptors depends not only on binding properties but also on opening/closing and desensitization. The impact of such functional coupling between channel states is critical in conditions of high non-equilibrium typical for synaptic transmission. The concentration dependence of the rising phase of the GABA-elicited current indicates positive cooperativity between agonist binding sites. We provide evidence that preequilibration at low GABA concentrations reduce GABA-evoked currents due to receptor trapping in a singly bound desensitized state.
Mozrzymas
Jerzy W
JW
Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland.
Barberis
Andrea
A
Mercik
Katarzyna
K
Zarnowska
Ewa D
ED
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002478:Cells, Cultured; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000187:drug effects* / Q000502:physiology; D007700:Kinetics; D009474:Neurons / Q000502:physiology*; D011487:Protein Conformation; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000737:chemistry / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid