Different pharmacological responses to CFTR inhibitor/blocker between zebrafish and human CFTR.

<p><b>(A)</b> and <b>(B)</b> Whereas 10 μM CFTR_inh-172 was reported to eliminate about 90% of WT-hCFTR current [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0209862#pone.0209862.ref052" target="_blank">52</a>], the same concentration of the reagent shows less inhibitory effect on WT-zCFTR. The virtually identical properties of both WT-zCFTR and WT-nzCFTR were confirmed at multiple points in the current study (e.g., Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0209862#pone.0209862.g001" target="_blank">1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0209862#pone.0209862.g002" target="_blank">2</a>) to avoid biased interpretations of our functional data because of potential changes in structure and function due to different protein translation rates caused by codon manipulations reported previously [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0209862#pone.0209862.ref054" target="_blank">54</a>]. <b>(C)</b> A representative whole-cell recording of WT-hCFTR in response to external application of 10 μM GlyH-101. In whole-cell recordings, right after break-in (a), the application 10 <b>μ</b>M forskolin elicits large CFTR current (b). A biphasic current drop upon the application of GlyH-101 was observed: an immediate decrease of the current (c) followed by a slow phase of current decrease (d). <b>(D)</b> Averaged fractions of unblock for both the fast phase (red) and the eventual steady-state (blue) from three recordings show voltage-dependence of external GlyH-101 block on WT-hCFTR. <b>(E)</b> A representative whole-cell recording of WT-zCFTR upon external application of 10 <b>μ</b>M GlyH-101. In addition to an abrupt current drop, a slow current decay was also observed. <b>(F)</b> Averaged fractions of unblock for both the fast phase (red) and the final block (blue) from three recordings show voltage-dependence of the fast block and voltage-independence of the final block on WT-zCFTR.</p>