The preference for ammonium may be attributed to a hyperpolarized membrane potential via TWIK-1 channels

Urine, which contains ammonium, transmits crucial signals among animals. However, the mechanism underlying signal transmission remains unknown. In our study, we observed that there are significant differences in olfactory preference depending on ammonium concentrations of 0.0004 %, 0.004 %, and 0.04 % between TWIK-1 gene knockout (TWIK-1^-/-) and wild-type (WT) mice (p < 0.05, n = 6), although there is no significant preference difference between the 4 % concentration groups. These results are consistent with calcium imaging data, which showed an increase in calcium fluorescence only in the olfactory epithelium (OE) of TWIK-1^-/- mice at 4 and 400 µM NH₄⁺ concentrations, but in both groups at 40 mM NH₄⁺. The electrophysiological results indicate an increase in the amplitudes of the inward current that hyperpolarizes the membrane potential at 400 µM NH₄⁺, while it depolarizes the membrane potential at higher NH₄⁺ concentrations. These findings suggest a potential mechanism by which ammonium hyperpolarizes the membrane potential via TWIK-1 channels at low concentrations, making the OE cells more difficult to activate and resulting in the differences in olfactory preference between the two groups.