PT  - JOURNAL ARTICLE
AU  - Lingke Zhao
AU  - Yen-Ping Kuo
AU  - Andrew A. George
AU  - Jian-Hong Peng
AU  - Madhuri Singh Purandare
AU  - Katherine M. Schroeder
AU  - Ronald J. Lukas
AU  - Jie Wu
TI  - Functional Properties of Homomeric, Human α7-Nicotinic Acetylcholine Receptors Heterologously Expressed in the SH-EP1 Human Epithelial Cell Line
AID  - 10.1124/jpet.103.048777
DP  - 2003 Jun 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1132--1141
VI  - 305
IP  - 3
4099  - http://jpet.aspetjournals.org/content/305/3/1132.short
4100  - http://jpet.aspetjournals.org/content/305/3/1132.full
SO  - J Pharmacol Exp Ther2003 Jun 01; 305
AB  - α7-Nicotinic acetylcholine receptors (α7-nAChRs) are broadly distributed in the central nervous system, where they play important roles in chemical and electrical signaling, and perhaps in neurite outgrowth, synaptic plasticity, and neuronal death/survival. To help elucidate their normal and pathophysiological roles, we have heterologously expressed human α7-nAChR in transfected SH-EP1 human epithelial cells. Reverse transcription-polymerase chain reaction and mRNA fluorescence in situ hybridization analyses demonstrate expression of human α7 subunits as messenger RNA. Patch-clamp recordings exploiting a novel strategy to prevent functional rundown of whole-cell peak current responses to repeated acute challenges with nicotinic agonists show successful expression of functional α7-nAChR that mediate inward currents characterized by rapid phases of activation and inactivation. Concentration-response curves show that nicotine, acetylcholine, and choline are efficacious agonists at human α7-nAChRs. Current-voltage relationships show inward rectification for agonist-induced currents. Human α7-nAChRs exhibit some sensitivity to α7-nAChR antagonists α-bungarotoxin (Bgt) or methyllycaconitine (MLA) when applied coincidentally with agonist, but much higher affinity block occurs when cells and α7-nAChRs are pre-exposed to antagonists for 2 min before challenge with agonist. Both Bgt and MLA are competitive inhibitors of α7-nAChR function. Whole-cell current peak amplitudes and half-times for inactivation of α7-nAChR functional responses to nicotine are dramatically reduced in the absence of extracellular Ca2+, suggestive of high Ca2+ permeability of the α7-nAChR channel. Thus, heterologously expressed human α7-nAChR in mammalian cells have properties of native α7-nAChR or of α7-nAChR heterologously expressed in other systems and serve as excellent models for studies of molecular bases of α7-nAChR function. The American Society for Pharmacology and Experimental Therapeutics