Fe²⁺-Mediated Activation of BK_Ca Channels by Rapid Photolysis of CORM-S1 Releasing CO and Fe²⁺

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 BK_Ca 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 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 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.