The correction of alpha7 nicotinic acetylcholine receptor concentration-response relationships in Xenopus oocytes

The rapid desensitization of alpha 7 nicotinic acetylcholine receptors (nAChR) has presented a serious problem for the characterization of this receptor subtype, potentially confounding the interpretation of concentration-response relationships. However, the consistency of cell geometry and solution flow in oocyte recordings permits estimations of instantaneous concentrations to be made in this system. Results interpreted with predicted instantaneous concentrations suggest that estimates of EC50 derived from conventional analysis may overestimate the actual EC50 values by a factor of 10 and underestimate Hill slopes by a factor of 2-3. If the limiting desensitization process of alpha 7 receptors is driven by the agonist concentration itself rather than by time-dependent processes, then similar dependencies may exist between the response and instantaneous agonist concentration in other systems. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.