Uchida Kunitoshi, Kita Tomo, Hatta Mitsutoki, Itoh Satoru G, Okumura Hisashi, Tominaga Makoto, Yamazaki Jun
Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Fukuoka, 814-0193, Japan.
Department of Environmental and Life Sciences, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Shizuoka, 422-8526, Japan.
Heliyon. 2021 Jan 29;7(1):e06102. doi: 10.1016/j.heliyon.2021.e06102. eCollection 2021 Jan.
The transient receptor potential melastatin 5 (TRPM5) channel is a monovalent-permeable cation channel that is activated by intracellular Ca. Expression of TRPM5 has been shown in taste cells, pancreas, brainstem and olfactory epithelium, and this channel is thought to be involved in controlling membrane potentials. In whole-cell patch-clamp recordings, TRPM5 exhibited voltage-dependent inactivation at negative membrane potentials and time constant of voltage-dependent inactivation of TRPM5 did not depend on the intracellular Ca concentrations between 100 and 500 nM. Alanine substitution at Y913 and I916 in the pore helix of TRPM5 increased time constant of voltage-dependent inactivation. Meanwhile, voltage-dependent inactivation was reduced in TRPM5 mutants having glycine substitution at L901, Y913, Q915 and I916 in the pore helix. From these results, we conclude that the pore helix in the outer pore loop might play a role in voltage-dependent inactivation of TRPM5.
瞬时受体电位香草素5（TRPM5）通道是一种单价阳离子通透通道，由细胞内钙离子激活。TRPM5已在味觉细胞、胰腺、脑干和嗅觉上皮中表达，该通道被认为参与控制膜电位。在全细胞膜片钳记录中，TRPM5在负膜电位下表现出电压依赖性失活，且TRPM5电压依赖性失活的时间常数在100至500 nM的细胞内钙浓度范围内不依赖于细胞内钙浓度。TRPM5孔螺旋中Y913和I916位点的丙氨酸取代增加了电压依赖性失活的时间常数。同时，在孔螺旋中L901、Y913、Q915和I916位点具有甘氨酸取代的TRPM5突变体中，电压依赖性失活减少。从这些结果中，我们得出结论，外孔环中的孔螺旋可能在TRPM5的电压依赖性失活中起作用。
