Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/44459
Title: A major interspecies difference in the ionic selectivity of megakaryocyte Ca <sup>2+</sup> -activated channels sensitive to the TMEM16F inhibitor CaCCinh-A01
Authors: Taylor, Kirk A.
Mahaut-Smith, Martyn P.
First Published: 22-Apr-2019
Publisher: Taylor & Francis
Citation: Platelets, 2019
Abstract: TMEM16F is a surface membrane protein critical for platelet procoagulant activity, which exhibits both phospholipid scramblase and ion channel activities following sustained elevation of cytosolic Ca 2+ . The extent to which the ionic permeability of TMEM16F is important for platelet scramblase responses remains controversial. To date, only one study has reported the electrophysiological properties of TMEM16F in cells of platelet/megakaryocyte lineage, which observed cation-selectivity within excised patch recordings from murine marrow-derived megakaryocytes. This contrasts with reports using whole-cell recordings that describe this channel as displaying either selectivity for anions or being relatively non-selective amongst the major physiological monovalent ions. We have studied TMEM16F expression and channel activity in primary rat and mouse megakaryocytes and the human erythroleukemic (HEL) cell line that exhibits megakaryocytic surface markers. Immunocytochemical analysis was consistent with surface TMEM16F expression in cells from all three species. Whole-cell recordings in the absence of K + -selective currents revealed an outwardly rectifying conductance activated by a high intracellular Ca 2+ concentration in all three species. These currents appeared after 5–6 minutes and were blocked by CaCC inh -A01, properties typical of TMEM16F. Ion substitution experiments showed that the underlying conductance was predominantly Cl – -permeable in rat megakaryocytes and HEL cells, yet non-selective between monovalent anions and cations in mouse megakaryocytes. In conclusion, the present study further highlights the difference in ionic selectivity of TMEM16F in platelet lineage cells of the mouse compared to other mammalian species. This provides additional support for the ionic “leak” hypothesis that the scramblase activity of TMEM16F does not rely upon its ability to conduct ions of a specific type.
DOI Link: 10.1080/09537104.2019.1595560
ISSN: 0953-7104
eISSN: 1369-1635
Links: https://www.tandfonline.com/doi/full/10.1080/09537104.2019.1595560
http://hdl.handle.net/2381/44459
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2019. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Description: Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/iplt
Appears in Collections:Published Articles, Dept. of Molecular and Cell Biology



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