TY - JOUR T1 - Determinants of Channel Gating Located in the N-Terminal Extracellular Domain of Nicotinic α7 Receptor JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 469 LP - 479 VL - 287 IS - 2 AU - René Anand AU - Mark E. Nelson AU - Volodymyr Gerzanich AU - Gregg B. Wells AU - Jon Lindstrom Y1 - 1998/11/01 UR - http://jpet.aspetjournals.org/content/287/2/469.abstract N2 - We identified regions within the N-terminal extracellular domain of α7 nicotinic acetylcholine receptors that affect channel gating. By single-channel analysis of α7 nicotinic acetylcholine receptors currents, we show that the difference in efficacy between the two agonists acetylcholine and 1,1-dimethyl-4-phenylpiperazinium (DMPP) is due to a slower channel activation rate by DMPP. The partial efficacy of DMPP was not caused by channel block or faster desensitization of α7 AChRs by DMPP. In addition, the efficacy and, by inference, the activation rate were found to be voltage dependent. Using chimeras of the two closely related subunits α7 and α8, we map residues that affect channel activation rate and agonist affinity to two different regions of the extracellular domain. Residues that affect channel activation rate are within the sequence 1–179, whereas residues that affect agonist affinity are within the sequence 180–208. The American Society for Pharmacology and Experimental Therapeutics ER -