2008
DOI: 10.1085/jgp.200810005
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Amphiphilic Blockers Punch through a Mutant CLC-0 Pore

Abstract: Intracellularly applied amphiphilic molecules, such as p-chlorophenoxy acetate (CPA) and octanoate, block various pore-open mutants of CLC-0. The voltage-dependent block of a particular pore-open mutant, E166G, was found to be multiphasic. In symmetrical 140 mM Cl−, the apparent affinity of the blocker in this mutant increased with a negative membrane potential but, paradoxically, decreased when the negative membrane potential was greater than −80 mV, a phenomenon similar to the blocker “punch-through” shown i… Show more

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Cited by 13 publications
(16 citation statements)
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“…2 above; see also [68]). High-voltage gating, sometimes called punch through [29, 92], is qualitatively consistent with the predominance of bulky, hydrophobic side chains within the pore, as depicted in Fig. 9b (left panel).…”
Section: Discussionsupporting
confidence: 63%
“…2 above; see also [68]). High-voltage gating, sometimes called punch through [29, 92], is qualitatively consistent with the predominance of bulky, hydrophobic side chains within the pore, as depicted in Fig. 9b (left panel).…”
Section: Discussionsupporting
confidence: 63%
“…This panel included flufenamic acid, the clofibric acid derivative 2-(p-chlorophenoxy)-3-(4-chlorophenyl)propionic acid, 9-anthracene carboxylate (9AC), 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), niflumic acid, octanoic acid, and 4,4′-diaminostilbene-2,2′-disulfonate (DADS) (Estevez, et al, 2003; Gradogna and Pusch, 2010; Venglarik, et al, 1994; Zhang and Chen, 2009). None of these compounds inhibited ClC-ec1; however, a modified compound (OADS) combining DADS with two aliphatic side chains mimicking the hydrophobic element of octanoic acid (Figure 1A) inhibited ClC-ec1 at low-micromolar concentrations.…”
Section: Resultsmentioning
confidence: 99%
“…S3 and S4 for more extensive explanations). Of note, this three-state blocking theme has been successfully used to account for the blocking mechanism of CLC-0 chloride channels as well as the “ball-and-chain” inactivation mechanism of potassium channels (Zhou et al, 2001; Zhang and Chen, 2009; Zhang et al, 2009, 2010).…”
Section: Discussionmentioning
confidence: 99%