Fe2+-Mediated Activation of BKCa Channels by Rapid Photolysis of CORM-S1 Releasing CO and Fe2+
journal contributionposted on 29.07.2020, 20:30 by Guido Gessner, Philipp Rühl, Matthias Westerhausen, Toshinori Hoshi, Stefan H. Heinemann
Heme catabolism by heme oxygenase (HO) with a decrease in intracellular heme concentration and a concomitant local release of CO and Fe2+ has the potential to regulate BKCa channels. Here, we show that the iron-based photolabile CO-releasing molecule CORM-S1 [dicarbonyl-bis(cysteamine)iron(II)] coreleases CO and Fe2+, making it a suitable light-triggered source of these downstream products of HO activity. To investigate the impact of CO, iron, and cysteamine on BKCa 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 Fe2+, Fe3+ and cysteamine possess only marginal activating potency. Investigation of hSlo1 mutants revealed that Fe2+ modulates the channels mainly through the Mg2+-dependent activation mechanism. Flash photolysis of CORM-S1 suits for rapid and precise delivery of Fe2+ and CO in biological settings.
Read the peer-reviewed publication
HEK 293T cellselectrophysiological methodsBKheme oxygenaseSlo 1Mediated ActivationRapid PhotolysisFeCORM-S 1 suitsFlash photolysishSlo 1 mutantshSlo 1 channelslight-triggered sourceHO activityactivation mechanismintracellular heme concentrationiron-based photolabile CO-releasing...CORM-S 1 Releasing CO