Purchase this article with an account.
P. Khalili, Y. Zhu, H. Qian; Picrotoxin Accelerates Relaxation of GABAC Receptor . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5142.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Picrotoxin is a commonly used agent that inhibits GABA and glycine receptors. However, the mechanisms of picrotoxin action are still in debate. In this study, we used GABAC receptor as a model system to probe the picrotoxin inhibition mechanisms. Methods: Xenopus oocytes were injected with cRNAs synthesized from cloned white perch GABA ρ subunit. Two-electrode voltage clamp recording techniques were used to monitor membrane currents from oocyte after 2-3 days of expression. Computer simulations of GABA and picrotoxin responses were performed with Matlab. Results: On oocytes expressing perch-ρ1A subunit, picrotoxin inhibited GABA-elicited currents both competitively and non-competitively, i.e. reducing both the maximum response amplitude and GABA sensitivity. GABA-elicited responses from ρ-receptor were characterized by their slow kinetics, especially the long time required for the current to return to the baseline after the termination of GABA application. When picrotoxin was co-applied with GABA, the amplitude of the elicited currents were much smaller than those elicited by GABA alone. After termination of GABA and picrotoxin, there was often a significant rebound of membrane current, which then gradually decayed back to baseline with a similar time course as the GABA-elicited currents. On the other hand, the presence of picrotoxin significantly altered the kinetics of GABA-elicited responses. In particular, the GABA relaxation was greatly accelerated by picrotoxin. From these data, we proposed a model for picrotoxin to bind the GABAC receptor in both channel open and closed states. Using parameters estimated from individual aspects of GABA response and picrotoxin inhibition, the model in whole provided a remarkably good approximation of all the properties of picrotoxin inhibition observed on the GABAC receptor. Conclusions: Our results suggest that picrotoxin could bind GABAC receptor in both channel open and closed conformations. Similar mechanisms are likely to account for picrotoxin inhibition on GABAA and glycine receptors.
This PDF is available to Subscribers Only