Single cilia, 100 nm in diameter and 10 µm in length, were isolated from mouse tracheae with Triton X-100 (0.02%) treatment, and the effects of pH on ciliary beating were examined by measuring the ciliary beat frequency (CBF) and the ciliary bend distance (CBD—an index of amplitude) using a high-speed video microscope (250 fps). ATP (2.5 mM) plus 8Br-cAMP (10 µM) reactivated the CBF and CBD in the isolated cilia, similar to the cilia of in vivo tracheae. In the reactivated isolated cilia, an elevation in pH from 7.0 to 8.0 increased the CBF from 3 to 15 Hz and the CBD from 0.6 to 1.5 µm. The pH elevation also increased the velocity of the effective stroke; however, it did not increase the recovery stroke, and, moreover, it decreased the intervals between beats. This indicates that H⁺ (pH_i) directly acts on the axonemal machinery to regulate CBF and CBD. In isolated cilia priorly treated with 1 µM PKI-amide (a PKA inhibitor), 8Br-cAMP did not increase the CBF or CBD in the ATP-stimulated isolated cilia. pH modulates the PKA signal, which enhances the axonemal beating generated by the ATP-activated inner and outer dyneins.

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

Background: The UCP1 A-3826G polymorphism, located in the gene’s regulatory region, is associated with obesity and altered fat metabolism. Because UCP1 plays a central role in thermogenesis, variation in its expression may influence metabolic efficiency and dietary fat preference. Methods: We examined associations between the A-3826G polymorphism and food preferences in healthy young Japanese adults (50 males, 48 females). Preferences for high-fat and basic-taste foods were assessed using a self-administered questionnaire, with sweet foods classified as low- or high-fat. Genotypes (AA, AG, GG) were analyzed using a two-way mixed-design ANOVA to evaluate genotype × fat level interactions. Results: Preference scores for basic tastes did not differ significantly among genotypes in either sex (except for sour taste in males). In males, no significant genotype × fat level interaction was observed, although AA carriers preferred high-fat to low-fat sweet foods (p < 0.05). In females, a significant genotype × fat level interaction was detected (p < 0.01), with AG carriers showing lower preference for high-fat sweet foods. Conclusions: These findings indicate that the UCP1 A-3826G polymorphism may modulate preference for high-fat sweet foods in a sex-dependent manner, suggesting a link between thermogenic genetic variation and dietary fat preference relevant to obesity prevention.

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.