Functional properties of homomeric, human α7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 human epithelial cell line

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.