A Molecular Link between Inward Rectification and Calcium Permeability of Neuronal Nicotinic Acetylcholine α3β4 and α4β2 Receptors

• DOI: 10.1523/jneurosci.20-02-00529.2000
• Publication Date: 2018-04-05T22:34:42Z
• Authors: Ali Pejmun Haghighi; Ellis Cooper
• Keywords: Calcium in biology

Many nicotinic acetylcholine receptors (nAChRs) expressed by central neurons are located at presynaptic nerve terminals. These have high calcium permeability and exhibit strong inward rectification, two important physiological features that enable them to facilitate transmitter release. Previously, we showed intracellular polyamines act as gating molecules block neuronal nAChRs in a voltage-dependent manner, leading rectification. Our goal is identify the structural determinants underlie govern of nAChRs. We hypothesize ring-like collections negatively charged amino acids (cytoplasmic intermediate rings) near mouth pore mediate interaction with also influence permeability. Using site-directed mutagenesis electrophysiology on α 4 β 2 3 Xenopus oocytes, observed removing five negative charges cytoplasmic ring had little effect either rectification or However, partial removal diminished high-affinity, between receptor, abolishing In addition, these nonrectifying mutant drastic reduction results indicate glutamic acid residues form both high-affinity binding site for selectivity filter inflowing ions; is, common links Physiologically, this molecular mechanism provides insight into how