Paradoxical Stimulation of a DEG/ENaC Channel by Amiloride
作者： Christopher M. Adams , Peter M. Snyder , Michael J. Welsh
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摘要: Extracellular amiloride inhibits all known DEG/ENaC ion channels, including BNC1, a proton-activated human neuronal cation channel. Earlier studies showed that protons cause conformational change activates BNC1 and exposes residue 430 to the extracellular solution. Here we demonstrate that, in addition blocking also 430. This result suggested like protons, might be capable of activating To test this hypothesis, introduced mutation pore reduces block, found stimulated these channels. Amiloride inhibition was voltage-dependent, suggesting block within pore, whereas stimulation not, binding an site. These data show can have two distinct effects on they suggest different interaction sites. The results may stimulatory effect similar or ligands other
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