Calcium-dependent decrease in the single-channel conductance of TRPV1.
Calcium-dependent decrease in the single-channel conductance of TRPV1.
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DOI：
10.1007/s00424-011-1013-7
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发表时间：
2011-11
影响因子：
4.5
通讯作者：
Egan, Terrance M.
中科院分区：
文献类型：
--
作者：
Samways, Damien S. K.;Egan, Terrance M.
TRPV1 is a Ca2+ permeable cation channel gated by multiple stimuli including noxious heat, capsaicin, protons, and extracellular cations. In this paper, we show that Ca2+ causes a concentration and voltage-dependent decrease in the capsaicin-gated TRPV1 single channel conductance. This Ca2+-dependent effect on conductance was strongest at membrane potentials between −60 mV and +20mV, but was diminished at more hyperpolarised potentials. Using simultaneous recordings of membrane current and fura-2 fluorescence to measure the fractional Ca2+ current of whole cell currents evoked through wild type and mutant TRPV1 receptor, we investigated a possible link between the mechanisms underlying Ca2+ permeation and the Ca2+-dependent effect on conductance. Surprisingly we found no evidence of a structural correlation, and observed that the substitution of amino acids known to regulate Ca2+ permeability had little effect on the ability for Ca2+ to decrease TRPV1 conductance. However, we did observe that the Ca2+-dependent effect on conductance was not diminished by negative hyperpolarization for a mutant receptor with severely impaired Ca2+ permeability, TRPV1-D646N/E648Q/E651Q. This would be consistent with the idea that Ca2+ reduces conductance by interacting with an intra-pore binding site, and that negative hyperpolarization reduces occupancy of this site by speeding the exit of Ca2+ into the cell. Taken together, our data show that in addition to directly and indirectly regulating channel gating, Ca2+ also directly reduces the conductance of TRPV1. Surprisingly, the mechanism underlying this Ca2+-dependent effect on conductance is largely independent of mechanisms governing Ca2+ permeability.
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影响因子：
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通讯作者：
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