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

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posted on 31.12.2018, 18:39 authored by Jingyao Zhang, Ying-Chun Yu, Jiunn-Tyng Yeh, Tzyh-Chang Hwang

(A) and (B) Whereas 10 μM CFTRinh-172 was reported to eliminate about 90% of WT-hCFTR current [52], 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 1 and 2) 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 [54]. (C) 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 μM 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). (D) 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. (E) A representative whole-cell recording of WT-zCFTR upon external application of 10 μM GlyH-101. In addition to an abrupt current drop, a slow current decay was also observed. (F) 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.

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