scholarly journals Expression and Possible Role of Nicotinic Acetylcholine Receptor ε Subunit (AChRe) in Mouse Sperm

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 46
Author(s):  
Yusei Makino ◽  
Yuuki Hiradate ◽  
Kohei Umezu ◽  
Kenshiro Hara ◽  
Kentaro Tanemura
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Acrosome Reaction ◽  
Sperm Function ◽  
Nicotinic Acetylcholine ◽  
Mouse Sperm ◽  
Mammalian Sperm ◽  
Specific Antagonist ◽  
Sperm Acrosome Reaction

The nicotinic acetylcholine receptor (nAChR) is one of the receptors of acetylcholine (ACh), and nicotine (NIC) acts as an agonist of this receptor. Among the nAChR subunits, we found that the ε subunit (AChRe) had approximately 10 to 1000 times higher level of mRNA expression in mouse testes than the other subunits. In this study, we aimed to elucidate the expression and localization of AChRe in the testes and spermatozoa of mice and clarify the effect of AChRe on sperm function. Immunocytochemistry showed that AChRe was expressed in the murine testes and spermatozoa. We found that AChRe was localized only in elongated spermatids from step 12 onwards in the testes. In spermatozoa, AChRe was localized in the head, especially in the anterior region of the acrosome, but only approximately 50% of spermatozoa showed this immunoreactivity. Additionally, we analyzed the effects of ACh and NIC on sperm acrosome reaction (AR) and found that both ACh and NIC suppressed the AR rate, which was restored by an AChRe-specific antagonist. These results suggest that AChRe may be a regulator of mammalian sperm AR.

scholarly journals Firing responses mediated via distinct nicotinic acetylcholine receptor subtypes in rat prepositus hypoglossi nuclei neurons

2018 ◽  
Vol 120 (4) ◽  
pp. 1525-1533
Author(s):  
Yue Zhang ◽  
Yuchio Yanagawa ◽  
Yasuhiko Saito
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Firing Frequency ◽  
Membrane Properties ◽  
Receptor Subtypes ◽  
Nicotinic Acetylcholine ◽  
Firing Patterns ◽  
Prepositus Hypoglossi ◽  
Specific Antagonist ◽  
The Relationship

We previously reported that cholinergic current responses mediated via nicotinic acetylcholine (ACh) receptors (nAChRs) in the prepositus hypoglossi nucleus (PHN), which participates in gaze control, can be classified into distinct types based on different kinetics and are mainly composed of α7- and/or non-α7-subtypes: fast (F)-, slow (S)-, and fast and slow (FS)-type currents. In this study, to clarify how each current type is related to neuronal activities, we investigated the relationship between the current types and the membrane properties and the firing responses that were induced by each current type. The proportion of the current types differed in neurons that exhibited different afterhyperpolarization (AHP) profiles and firing patterns, suggesting that PHN neurons show a preference for specific current types dependent on the membrane properties. In response to ACh, F-type neurons showed either one action potential (AP) or multiple APs with a short firing duration, and S-type neurons showed multiple APs with a long firing duration. The firing frequency of F-type neurons was significantly higher than that of S-type and FS-type neurons. An α7-subtype-specific antagonist abolished the firing responses of F-type neurons and reduced the responses of FS-type neurons but had little effect on the responses of S-type neurons, which were reduced by a non-α7-subtype-specific antagonist. These results suggest that the different properties of the current types and the distinct expression of the nAChR subtypes in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs. NEW & NOTEWORTHY Prepositus hypoglossi nucleus (PHN) neurons show distinct nicotinic acetylcholine receptor (nAChR)-mediated current responses. The proportion of the current types differed in the neurons that exhibited different afterhyperpolarization profiles and firing patterns. The nAChR-mediated currents with different kinetics induced firing responses of the neurons that were distinct in the firing frequency and duration. These results suggest that the different properties of the current types in PHN neurons with different membrane properties produce unique firing responses via the activation of nAChRs.

scholarly journals The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and coevolutionary analyses

2020 ◽  
Vol 295 (32) ◽  
pp. 11056-11067 ◽  
Author(s):  
Mackenzie J. Thompson ◽  
Jaimee A. Domville ◽  
John E. Baenziger
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Site Directed Mutagenesis ◽  
Induced Response ◽  
Independent Manner ◽  
Nicotinic Acetylcholine ◽  
Α Subunit ◽  
Lipid Sensing ◽  
Insight Into

The activity of the muscle-type Torpedo nicotinic acetylcholine receptor (nAChR) is highly sensitive to lipids, but the underlying mechanisms remain poorly understood. The nAChR transmembrane α-helix, M4, is positioned at the perimeter of each subunit in direct contact with lipids and likely plays a central role in lipid sensing. To gain insight into the mechanisms underlying nAChR lipid sensing, we used homology modeling, coevolutionary analyses, site-directed mutagenesis, and electrophysiology to examine the role of the α-subunit M4 (αM4) in the function of the adult muscle nAChR. Ala substitutions for most αM4 residues, including those in clusters of polar residues at both the N and C termini, and deletion of up to 11 C-terminal residues had little impact on the agonist-induced response. Even Ala substitutions for coevolved pairs of residues at the interface between αM4 and the adjacent helices, αM1 and αM3, had little effect, although some impaired nAChR expression. On the other hand, Ala substitutions for Thr422 and Arg429 caused relatively large losses of function, suggesting functional roles for these specific residues. Ala substitutions for aromatic residues at the αM4-αM1/αM3 interface generally led to gains of function, as previously reported for the prokaryotic homolog, the Erwinia chrysanthemi ligand-gated ion channel (ELIC). The functional effects of individual Ala substitutions in αM4 were found to be additive, although not in a completely independent manner. Our results provide insight into the structural features of αM4 that are important. They also suggest how lipid-dependent changes in αM4 structure ultimately modify nAChR function.

Sign in / Sign up

Export Citation Format

Share Document