Questions: 

Breakdown of heme is catalyzed by hemoxygenase (HMOX) resulting in biliverdin, carbon monoxide (CO) and iron ions (Fe). The latter two breakdown products are important signaling molecules with a multitude of physiological effects. To systematically study the effects of CO and Fe²⁺, a precise and rapid delivery method is required. We thus aimed to introduce a light-triggered CO- and Fe²⁺-releasing molecule for physiological applications.

Methods: 

CORM-S1 (dicarbonyl-bis(cysteamine)iron(II)) was synthesized and CO-release was quantified with a spectroscopic myoglobin assay (Kretschmer et al., 2011, J. Inorg. Biochem. 105, 6–9). Human Slo1 voltage and Ca²⁺-activated BK potassium channels (KCa1.1) were expressed in HEK 293 cells and analyzed in excised inside-out patches. CO and Fe²⁺ release from CORM-S1 added to the bath solution in the dark were triggered with various light sources.

Results: 

CORM-S1 rapidly released both CO and Fe²⁺ when irradiated with visible light. CO liberated from CORM-S1 activated BK channels similar to CO-saturated solutions. However, light-induced release permitted rapid and precise "CO-mediated gating". Moreover, Fe²⁺ released from CORM-S1 also exerted a strong activating effect on BK channels when recording in EGTA-free, fluoride-buffered solutions. This effect was independent of CO because a CO-insensitive mutant of Slo1 BK was affected in a similar manner.

Conclusions: 

CORM-S1 is a useful agent to deliver CO and Fe²⁺ in a physiological setting using visible light as a trigger. CO released from CORM-S1 activates BK channels rapidly and reversibly. Moreover, Fe²⁺ is a secondary activator of BK channels. Since hemoxygenase and BK channels may form a complex, local generation of CO and Fe²⁺ is expected to modulate BK channel activity in vivo.