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J Neurophysiol (February 1, 2003). 10.1152/jn.00951.2002
Submitted on Submitted 23 October 2002; accepted in final form 23 October 2002
arnowska1
1Department of Biophysics, Wroclaw Medical University, 50-368 Wroclaw, Poland; 2Neuroscience Program and Istituto Nazionale Fisica della Materia (INFM) Unit, International School for Advanced Studies (SISSA), 34-014 Trieste, Italy; and 3Institute of Physics, Technical University of Wroclaw, 50-370 Wroclaw, Poland
Mozrzymas, Jerzy W.,
Andrea Barberis,
Katarzyna Mercik, and
Ewa
D. arnowska.
Binding Sites, Singly Bound States, and Conformation Coupling
Shape GABA-Evoked Currents. J. Neurophysiol. 89: 871-883, 2003. The time course of GABA-evoked currents
is the main source of information on the GABAA
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
GABAA 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.
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