期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 100, 期 25, 页码 15166-15171出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2334624100
关键词
-
资金
- NIGMS NIH HHS [R01-GM065360, R01 GM065360, R01 GM063954, R01-GM63954] Funding Source: Medline
- NINDS NIH HHS [R01-NS040927, R01 NS040927] Funding Source: Medline
Transient receptor potential (TRIP) proteins are a diverse family of proteins with structural features typical of ion channels. TRPM5, a member of the TRPM subfamily, plays an important role in taste receptors, although its activation mechanism remains controversial and its function in signal transduction is unknown. Here we characterize the functional properties of heterologously expressed human TRPM5 in HEK-293 cells. TRPM5 displays characteristics of a calcium-activated, nonselective cation channel with a unitary conductance of 25 pS. TRPM5 is a monovalent-specific, nonselective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca2+ ions. It is directly activated by [Ca2+](i) at concentrations of 0.3-1 muM, whereas higher concentrations are inhibitory, resulting in a bell-shaped dose-response curve. It activates and deactivates rapidly even during sustained elevations in [Ca2+](i), thereby inducing a transient membrane depolarization. TRPM5 does not simply mirror levels of [Ca2+]i, but instead responds to the rate of change in [Ca2+], in that it requires rapid changes in [Ca2+]i to generate significant whole-cell currents, whereas slow elevations in [Ca2+], to equivalent levels are ineffective. Moreover, we demonstrate that TRPM5 is not limited to taste signal transduction, because we detect the presence of TRPM5 in a variety of tissues and we identify endogenous TRPM5-like currents in a pancreatic beta cell line. TRPM5 can be activated physiologically by inositol 1,4,5-trisphosphate-producing receptor agonists, and it may therefore couple intracellular Ca2+ release to electrical activity and subsequent cellular responses.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据