Objective: Cyclic adenosine monophosphate (cAMP) and cyclic nucleotide-gated (CNG) channels play an important role in olfactory perception. The purpose of this study was to explore the effect of glucocorticoid on the CNG channels of olfactory receptor neurons (ORNs).
Methods: For in vivo studies, rats were injected with dexamethasone 1 mg/kg body weight intraperitoneally once or once a day for 2 weeks. After 24 hours or 2 weeks, the difference in CNGA2 (the principal subunit of CNG channels) messenger ribonucleic acid (mRNA) in the ORNs was detected. For in vitro studies, the ORN membrane was extracted and incubated with 0.1 or 1 mg/mL dexamethasone for 5 or 30 minutes, respectively, and then the concentrations of cAMP were measured. For all experiments, normal saline was used as the control.
Results: For in vivo studies, compared with the normal saline group, CNGA2 mRNA could be upregulated in the 2-week group (p < .01) but not in the 24-hour group (p > .05). For in vitro studies, dexamethasone of both 0.1 and 1 mg/mL raised the concentration of cAMP in the ORNs at 5 and 30 minutes, respectively (p < .05), and the concentration of cAMP was higher in the 1 mg/mL groups than in the 0.1 mg/mL groups (p < .05). However, there was no significant difference between the 5-minute and 30-minute groups with either concentration.
Conclusions: Glucocorticoid enhanced both the mRNA expression of CNG channels and the production of cAMP, which might be a possible pathway for treating olfactory disorders. The effect of glucocorticoid was dose-dependent.
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Elife
December 2024
Department of Physiology and Biophysics, University of Washington, Seattle, United States.
Cyclic nucleotide-binding domain (CNBD) ion channels play crucial roles in cellular-signaling and excitability and are regulated by the direct binding of cyclic adenosine- or guanosine-monophosphate (cAMP, cGMP). However, the precise allosteric mechanism governing channel activation upon ligand binding, particularly the energetic changes within domains, remains poorly understood. The prokaryotic CNBD channel SthK offers a valuable model for investigating this allosteric mechanism.
View Article and Find Full Text PDFCurr Biol
November 2024
Life Sciences Institute, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address:
Shear stress sensing represents a vital mode of mechanosensation. Previous efforts have mainly focused on characterizing how various cell types-for example, vascular endothelial cells-sense shear stress arising from fluid flow within the animal body. How animals sense shear stress derived from their external environment, however, is not well understood.
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October 2024
Jiangxi Provincial Key Laboratory of Natural Active Pharmaceutical Constituents, Department of Chemistry and Bioengineering, Yichun University, Yichun, China.
Mammalian sperm are characterized as specialized cells, as their transcriptional and translational processes are largely inactive. Emerging researches indicate that Ca serves as a crucial second messenger in the modulation of various sperm physiological processes, such as capacitation, hyperactivation, and the acrosome reaction. Specifically, sperm-specific calcium channels, including CatSper, voltage-gated calcium channels (VGCCs), store-operated calcium channels (SOCCs), and cyclic nucleotide-gated (CNG) channels, are implicated in the regulation of calcium signaling in mammalian sperm.
View Article and Find Full Text PDFbioRxiv
October 2024
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195.
Cyclic nucleotide-binding domain (CNBD) ion channels play crucial roles in cellular-signaling and excitability and are regulated by the direct binding of cyclic adenosine- or guanosine-monophosphate (cAMP, cGMP). However, the precise allosteric mechanism governing channel activation upon ligand binding, particularly the energetic changes within domains, remains poorly understood. The prokaryotic CNBD channel SthK offers a valuable model for investigating this allosteric mechanism.
View Article and Find Full Text PDFNat Commun
September 2024
Department of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, New York, NY, USA.
The signaling lipid phosphatidylinositol-4,5-bisphosphate (PIP2) regulates many ion channels. It inhibits eukaryotic cyclic nucleotide-gated (CNG) channels while activating their relatives, the hyperpolarization-activated and cyclic nucleotide-modulated (HCN) channels. The prokaryotic SthK channel from Spirochaeta thermophila shares features with CNG and HCN channels and is an established model for this channel family.
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