Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A decrease in ciliary motility induced by a CO2/HCO3--free solution characteristic of ciliated human nasal epithelial cells: acceleration of HCO3- transport by carbonic anhydrase IV

Version 1 : Received: 26 June 2024 / Approved: 28 June 2024 / Online: 28 June 2024 (06:07:12 CEST)

How to cite: Okamoto, S.; Yasuda, M.; Kawaguchi, K.; Yasuoka, K.; Kikukawa, Y.; Asano, S.; Tsujii, T.; Inoue, S.; Amagase, K.; Inui, T.-A.; Hirano, S.; Inui, T.; Marunaka, Y.; Nakahari, T. A decrease in ciliary motility induced by a CO2/HCO3--free solution characteristic of ciliated human nasal epithelial cells: acceleration of HCO3- transport by carbonic anhydrase IV. Preprints 2024, 2024062013. https://doi.org/10.20944/preprints202406.2013.v1 Okamoto, S.; Yasuda, M.; Kawaguchi, K.; Yasuoka, K.; Kikukawa, Y.; Asano, S.; Tsujii, T.; Inoue, S.; Amagase, K.; Inui, T.-A.; Hirano, S.; Inui, T.; Marunaka, Y.; Nakahari, T. A decrease in ciliary motility induced by a CO2/HCO3--free solution characteristic of ciliated human nasal epithelial cells: acceleration of HCO3- transport by carbonic anhydrase IV. Preprints 2024, 2024062013. https://doi.org/10.20944/preprints202406.2013.v1

Abstract

An application of CO2/HCO3--free solution (Zero-CO2) did not increase intracellular pH (pHi) in ciliated human nasal epithelial cells (c-hNECs), leading to no increase in the beating frequency (CBF) or bend distance (CBD, an index of amplitude). This study demonstrated that the pHi of the c-hNECs expressing carbonic anhydrase IV (CAIV) is high (7.64), while that of the ciliated human bronchial epithelial cells (c-hBECs) expressing no CAIV is low (7.10). Upon applying Zero-CO2, an extremely high level of pHi caused the pHi, CBF and CBD to decrease, while a low level of pHi caused them to increase. The high pHi was generated by a high rate of HCO3- influx via interac-tions between CAIV and Na+/HCO3- cotransport (NBC) in c-hNECs. An NBC inhibitor (S0859) decreased the pHi and CBF, and Zero-CO2 application increased the CBF in S0859-treated c-hNECs. In conclusion, the interactions of CAIV and NBC maximize the HCO3- influx to increase the pHi in c-hNECs. This novel mechanism causes the pHi to decrease, leading to no increase in CBF and CBD in c-hNECs upon Zero-CO2 application, and appears to play a crucial role in maintaining pHi, CBF and CBD in c-hNECs periodically exposed to air (0.04% CO2) with respiration.

Keywords

nasal cilia; intracellular pH; NH4+ pulse; NBC; bicarbonate transport metabolon; airway; ALI; ciliary motility; ciliary waveform; CBF

Subject

Medicine and Pharmacology, Otolaryngology

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