Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Gessner G

PROVIDER: S-EPMC7442670 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Gessner Guido G Rühl Philipp P Westerhausen Matthias M Hoshi Toshinori T Heinemann Stefan H SH

ACS chemical biology 20200729 8

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 B ...[more]

PMID: 32667185

Similar Datasets

Project description:Mammalian circadian (24 h) rhythms are timed by the pattern of spontaneous action potential firing in the suprachiasmatic nucleus (SCN). This oscillation in firing is produced through circadian regulation of several membrane currents, including large-conductance Ca2+- and voltage-activated K+ (BK) and L-type Ca2+ channel (LTCC) currents. During the day steady-state BK currents depend mostly on LTCCs for activation, whereas at night they depend predominantly on ryanodine receptors (RyRs). However, the contribution of these Ca2+ channels to BK channel activation during action potential firing has not been thoroughly investigated. In this study, we used a pharmacological approach to determine that both LTCCs and RyRs contribute to the baseline membrane potential of SCN action potential waveforms, as well as action potential-evoked BK current, during the day and night, respectively. Since the baseline membrane potential is a major determinant of circadian firing rate, we focused on the LTCCs contributing to low voltage activation of BK channels during the subthreshold phase. For these experiments, two LTCC subtypes found in SCN (CaV1.2 and CaV1.3) were coexpressed with BK channels in heterologous cells, where their differential contributions could be separately measured. CaV1.3 channels produced currents that were shifted to more hyperpolarized potentials compared with CaV1.2, resulting in increased subthreshold Ca2+ and BK currents during an action potential command. These results show that although multiple Ca2+ sources in SCN can contribute to the activation of BK current during an action potential, specific BK-CaV1.3 partnerships may optimize the subthreshold BK current activation that is critical for firing rate regulation.NEW & NOTEWORTHY BK K+ channels are important regulators of firing. Although Ca2+ channels are required for their activation in excitable cells, it is not well understood how BK channels activate using these Ca2+ sources during an action potential. This study demonstrates the differences in BK current activated by CaV1.2 and CaV1.3 channels in clock neurons and heterologous cells. The results define how specific ion channel partnerships can be engaged during distinct phases of the action potential.

Dataset Information

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

Publications

Fe<sup>2+</sup>-Mediated Activation of BK<sub>Ca</sub> Channels by Rapid Photolysis of CORM-S1 Releasing CO and Fe<sup>2</sup>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets