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Molecular determinants of differential pore blocking of kidney CLC-K chloride channels
No full textThe highly homologous Cl(-) channels CLC-Ka and CLC-Kb are important for water and salt conservation in the kidney and for the production of endolymph in the inner ear. Mutations in CLC-Kb lead to Bartter's syndrome and mutations in the small CLC-K subunit barttin lead to Bartter's syndrome and deafness. Here we show that CLC-Ka is blocked by the recently identified blocker 2-(p-chlorophenoxy)-3-phenylpropionic acid of the rat channel CLC-K1 with an apparent K(D) approximately 80 microM. We also found that DIDS (4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid), a generic Cl(-) channel blocker, inhibits CLC-Ka (K(D) approximately 90 microM). Surprisingly, the highly homologous channel CLC-Kb is fivefold to sixfold less sensitive to both compounds. Guided by the crystal structure of bacterial CLC proteins, we identify two amino acids, N68/D68 and G72/E72, in CLC-Ka and CLC-Kb, respectively, that are responsible for the differential drug sensitivity. Both residues expose their side chains in the extracellular pore mouth, delineating the probable drug binding site. These novel CLC-K channel blockers are promising lead compounds for the development of new diuretic drugs
Different flecainide sensitivity of hNav1.4 channels and myotonic mutants explained by state-dependent block
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Renal CLC-K chloride channels heterologously coexpressed with barttin are specifically affected by 2-(p-chlorophenoxy)propionic acid derivatives
No full textNiflumic acid derivatives modulate macroscopic chloride conductance of native rat skeletal muscle by inhibiting the CLC-1 channel and by increasing the intracellular calcium level
No full textIndependent impairment of chloride channel function and calcium homeostasis in dystrophic muscle of exercised MDX mouse
No full textSimulated microgravity modifies the activity of protein kinase C and serine-threonine phosphatase controlling the resting chloride channel conductance in skeletal muscle
No full textNiflumic acid derivatives modulate macroscopic chloride conductance of native rat skeletal muscle by inhibiting the CLC-1 channel and by increasing the intracellular calcium level
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Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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