Rapidly photoreleased Fe2+ activates BK channels

Gessner, G., P. Rühl., M. Westerhausen, T. Hoshi, S.H. Heinemann. Fe2+-mediated activation of BKCa channels by rapid photolysis of CORM-S1 releasing CO and Fe2+. ACS Chemical Biology (2020) 15(8): 2098-2106​

CORM-S1 releases CO and Fe2+, both of which activate BK channels

Illustration: FSU Biophysik

Catabolism of heme by heme oxygenase results in the liberation of carbon monoxide (CO) and iron ions (Fe2+). Studying the impact of both mediators is not straightforward because of rapid diffusion and limited stability. Here we demonstrate that CORM-S1 (dicarbonyl-bis(cysteamine)iron(II)) is a useful chemical that precisely delivers CO and Fe2+ when illuminated with blue light. Fe2+, rapidly released from CORM-S1 in a flash-photolysis setting, activates BKCa channels with an efficacy much higher than CO. BKCa channels are therefore downstream targets of heme oxygenase and may connect heme signaling with electrical cell signaling. Physiologically relevant micromolar Fe2+ concentrations activate BKCa channels as much as unphysiologically high (> 2 mM) Mg2+ concentrations.