Dataset Information

BK_Ca (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster.

ABSTRACT: BK_Ca channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BK_Ca channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BK_Ca channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BK_Ca channels are present in fly mitochondria, and slo mutants show structural and functional defects in mitochondria. slo mutants display an increase in reactive oxygen species and the modulation of ROS affected their survival. We also found that the absence of BK_Ca channels reduced the lifespan of Drosophila, and overexpression of human BK_Ca channels in flies extends life span in males. Our study establishes the presence of BK_Ca channels in mitochondria of Drosophila and ascertains its novel physiological role in regulating mitochondrial structural and functional integrity, and lifespan.

SUBMITTER: Gururaja Rao S

PROVIDER: S-EPMC6770356 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

BKCa (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster.

Gururaja Rao Shubha S Bednarczyk Piotr P Towheed Atif A Shah Kajol K Karekar Priyanka P Ponnalagu Devasena D Jensen Haley N HN Addya Sankar S Reyes Beverly A S BAS Van Bockstaele Elisabeth J EJ Szewczyk Adam A Wallace Douglas C DC Singh Harpreet H

Cells 20190821 9

BKCa channels, originally discovered in Drosophila melanogaster as slowpoke (slo), are recognized for their roles in cellular and organ physiology. Pharmacological approaches implicated BKCa channels in cellular and organ protection possibly for their ability to modulate mitochondrial function. However, the direct role of BKCa channels in regulating mitochondrial structure and function is not deciphered. Here, we demonstrate that BKCa</s ...[more]

PMID: 31438578

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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

BK_Ca (Slo) Channel Regulates Mitochondrial Function and Lifespan in Drosophila melanogaster.

Publications

BK<sub>Ca</sub> (<i>Slo</i>) Channel Regulates Mitochondrial Function and Lifespan in <i>Drosophila melanogaster</i>.

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