Membrane voltage modulates the GABA(A) receptor gating in cultured rat hippocampal neurons.

Laboratory of Neuroscience, Department of Biophysics, Wrocław Medical University, ul. Chałubińskiego 3, 50-368 Wrocław, Poland.
Neuropharmacology (Impact Factor: 4.82). 03/2006; 50(2):143-53. DOI: 10.1016/j.neuropharm.2005.08.001
Source: PubMed

ABSTRACT The kinetics of GABAergic currents in neurons is known to be modulated by the membrane voltage but the underlying mechanisms have not been fully explored. In particular, the impact of membrane potential on the GABA(A) receptor gating has not been elucidated. In the present study, the effect of membrane voltage on current responses elicited by ultrafast GABA applications was studied in cultured hippocampal neurons. The current to voltage relationship (I-V) for responses to saturating [GABA] (10 mM) showed an inward rectification (slope conductance at positive voltages was 0.62 +/- 0.05 of that at negative potentials). On the contrary, I-V for currents evoked by low [GABA] (1 microM) showed an outward rectification. The onset of currents elicited by saturating [GABA] was significantly accelerated at positive potentials. Analysis of currents evoked by prolonged applications of saturating [GABA] revealed that positive voltages significantly increased the rate and extent of desensitization. The onsets of current responses to non-saturating [GABA] were significantly accelerated at positive voltages indicating an enhancement of the binding rate. However, at low [GABA] at which the onset rate is expected to approach an asymptote set by opening/closing and unbinding rates, no significant modification of current onset by voltage was observed. Quantitative analysis based on model simulations indicated that the major effect of membrane depolarization was to increase the rates of binding, desensitization and of opening as well as to slightly reduce the rate of exit from desensitization. In conclusion, we provide evidence that membrane voltage affects the GABA(A) receptor microscopic gating.

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    • "The rationale for accepting such a functional difference stems from the fact that the ion channel has been reported to be a simple ohmic pore, conducting anions equally well in both directions across the membrane (Bormann , 1988; Angelotti and Macdonald, 1993). It has been reported that the ion channel exhibits varying degrees of rectification (Krishek and Smart, 2001; Pytel et al., 2006; Pavlov et al., 2009), which may not be attributable simply to asymmetry in the chloride concentration across the membrane , as predicted by the constant field equation (Goldman, This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant GM0739591]. "
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