Open AccessFe2+-Mediated Activation of BKCa Channels by Rapid Photolysis of CORM-S1 Releasing CO and Fe2+
Author(s) -
Guido Geßner,
Philipp Rühl,
Matthias Westerhausen,
Toshinori Hoshi,
Stefan Heinemann
Publication year - 2020
Publication title -
acs chemical biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.899
H-Index - 111
eISSN - 1554-8937
pISSN - 1554-8929
DOI - 10.1021/acschembio.0c00282
Subject(s) - cysteamine , chemistry , heme , heme oxygenase , biophysics , flash photolysis , mutant , photodissociation , intracellular , hek 293 cells , biochemistry , photochemistry , kinetics , enzyme , biology , physics , quantum mechanics , gene , reaction rate constant
Heme catabolism by heme oxygenase (HO) with a decrease in intracellular heme concentration and a concomitant local release of CO and Fe 2+ has the potential to regulate BK Ca channels. Here, we show that the iron-based photolabile CO-releasing molecule CORM-S1 [dicarbonyl-bis(cysteamine)iron(II)] coreleases CO and Fe 2+ , making it a suitable light-triggered source of these downstream products of HO activity. To investigate the impact of CO, iron, and cysteamine on BK Ca channel activation, human Slo1 (hSlo1) was expressed in HEK293T cells and studied with electrophysiological methods. Whereas hSlo1 channels are activated by CO and even more strongly by Fe 2+ , Fe 3+ and cysteamine possess only marginal activating potency. Investigation of hSlo1 mutants revealed that Fe 2+ modulates the channels mainly through the Mg 2+ -dependent activation mechanism. Flash photolysis of CORM-S1 suits for rapid and precise delivery of Fe 2+ and CO in biological settings.