Ligand-specific temperature-dependent shifts in EC50 values for the GABA(A) receptor

Journal article, 2008

We introduce a system for temperature control of a commercial microfluidic superfusion device that, in combination with patch-clamp, enables rapid acquisition of dose-response data at different temperatures. We obtained dose-response curves for the GABA A receptor, a ligand-gated ion channel, for two different agonists at temperatures between 25 and 40°C. For GABA, the dose-response curves shifted toward higher EC 50 values as the temperature increased, whereas for/?-alanine, the EC 50 values were constant. This shows that temperature is an important factor for obtaining accurate estimations of EC 50 values and also that such temperature effects can be ligand-specific. Using the EC 50 values, we estimated the enthalpy of dissociation between the ligand and the receptor. Furthermore, the technology introduced here is generally applicable to all patch-clamp studies where temperature control is desirable, e.g., studies of kinetics and thermodynamics, drug screening, compliant ADME/Tox testing, and in studies of temperature-gated ion channels. © 2008 American Chemical Society.