Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice
Adaptive downregulation of a quinidine-sensitive cation conductance in renal principal cells of TWIK-1 knockout mice
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DOI：
10.1007/s00424-006-0107-0
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发表时间：
2006-10-01
影响因子：
4.5
通讯作者：
Robson, L.
中科院分区：
文献类型：
--
作者：
Millar, I. D.;Taylor, H. C.;Robson, L.
TWIK-1, a member of the two-pore domain K+ channel family, is expressed in brain, kidney, and lung. The aim of this study was to examine the effect of loss of TWIK-I on the renal cortical collecting duct. Ducts were isolated from wild-type and TWIK-1 knockout mice by enzyme digestion and whole-cell clamp obtained via the basolateral membrane. Current- and voltage-clamp approaches were used to examine K+ conductances. No difference was observed between intercalated cells from wild-type or knockout ducts. In contrast, knockout principal cells were hyperpolarized compared to wild-type cells and had a reduced membrane conductance. This was a consequence of a fall in a barium-insensitive, quinidine-sensitive conductance (G(Quin)). G(Quin), demonstrated outward rectification and had a relatively low K+ to Na+ selectivity ratio. Loss of GQuin would be expected to lead to the hyperpolarization observed in knockout ducts by increasing fractional K+ conductance and Na+ uptake by the cell. Consistent with this hypothesis, knockout ducts had an increased diameter in comparison to wild-type ducts. These data suggest that G(Quin) contributes to the resting membrane potential in the cortical collecting duct and that a fall in G(Quin) could be an adaptive response in TWIK-1 knockout ducts.
