期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 22, 页码 8752-8757出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1117433109
关键词
patch clamp; calcium imaging
资金
- National Eye Institute [EY010254]
- Research to Prevent Blindness
- National Natural Science Foundation of China [81000395]
- State Key Laboratory of Medical Neurobiology, Fudan University [10-02]
- Wuhan University
ON bipolar cells are critical for the function of the ON pathway in the visual system. They express a metabotropic glutamate receptor (mGluR6) that, when activated, couples to the G(o) class of G protein. The channel that is primarily responsible for the synaptic response has been recently identified as the transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1 is negatively coupled to the mGluR6/Go cascade such that activation of the cascade results in closure of the channel. Light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein activation in the dark is a critical step in the process of ON bipolar cell signal transduction, but the precise pathway linking these two events is not understood. To address this question, we measured TRPM1 activity in retinal bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the G beta gamma subunit dimer, but not G alpha(o), closed TRPM1 channels in every cell type that we tested. In addition, activation of an endogenous G-protein-coupled receptor pathway in HEK293 cells that releases G beta gamma. without activating Go protein also closed TRPM1 channels. These results suggest a model in which the G beta gamma. dimer that is released as a result of the dissociation from G alpha(o) upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction.
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