Opening of Intermediate Conductance Ca<sup>2+</sup>-Activated K<sup>+</sup> Channels in C2C12 Skeletal Muscle Cells Increases the Myotube Diameter via the Akt/Mammalian Target of Rapamycin Pathway

Iseki, Yuzo; Ono, Yuko; Hibi, Chihiro; Tanaka, Shoko; Takeshita, Shunya; Maejima, Yuko; Kurokawa, Junko; Murakawa, Masahiro; Shimomura, Kenju; Sakamoto, Kazuho

doi:10.1124/jpet.120.000290

Cited by 5 publications

(5 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Administration of the Ca 2+ -activated K + channel opener DCEBIO facilitates muscle differentiation and causes hypertrophy in differentiating C2C12 myoblast cells. These effects were mediated by mitochondrial IK channels, and the increased phosphorylation level of Akt, a known skeletal muscle hypertrophy factor [ 173 ].…”

Section: Calcium-dependent Potassium Channelsmentioning

confidence: 99%

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Takács

Kovács

Ebeid

et al. 2023

IJMS

View full text Add to dashboard Cite

Musculoskeletal disorders represent one of the main causes of disability worldwide, and their prevalence is predicted to increase in the coming decades. Stem cell therapy may be a promising option for the treatment of some of the musculoskeletal diseases. Although significant progress has been made in musculoskeletal stem cell research, osteoarthritis, the most-common musculoskeletal disorder, still lacks curative treatment. To fine-tune stem-cell-based therapy, it is necessary to focus on the underlying biological mechanisms. Ion channels and the bioelectric signals they generate control the proliferation, differentiation, and migration of musculoskeletal progenitor cells. Calcium- and voltage-activated potassium (KCa) channels are key players in cell physiology in cells of the musculoskeletal system. This review article focused on the big conductance (BK) KCa channels. The regulatory function of BK channels requires interactions with diverse sets of proteins that have different functions in tissue-resident stem cells. In this narrative review article, we discuss the main ion channels of musculoskeletal stem cells, with a focus on calcium-dependent potassium channels, especially on the large conductance BK channel. We review their expression and function in progenitor cell proliferation, differentiation, and migration and highlight gaps in current knowledge on their involvement in musculoskeletal diseases.

show abstract

Section: Calcium-dependent Potassium Channelsmentioning

confidence: 99%

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Takács

Kovács

Ebeid

et al. 2023

IJMS

View full text Add to dashboard Cite

show abstract

“…Subsequently, we examined the effects of TJ-41 on C2C12 morphology. Following the method adopted in previous studies [32][33][34], multiple myotubes from each experiment were counted as samples, then their width was measured and statistically compared. The deprivation of serum for 48 h resulted in a decrease in myotube width, whereas TJ-41 treatment significantly inhibited this decrease in width (Fig.…”

Section: Tj-41 Downregulated Atrogin-1 In C2c12 Myotubesmentioning

confidence: 99%

Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro

Yakabe

Hosoi

Sasakawa

et al. 2022

BMC Complement Med Ther

View full text Add to dashboard Cite

Background Muscle disuse results in loss of skeletal muscle mass and function. Hochu-ekki-to (TJ-41; Bu-Zhong-Yi-Qi-Tang in Chinese) is an herbal medicinal formulation used to treat patients with frailty, fatigue and appetite loss. It has been suggested that two atrogenes, atrogin-1 and muscle Ring finger 1 (MuRF1), are ubiquitin ligases involved in disuse-induced muscle atrophy and that 5’ adenosine monophosphate-activated protein kinase (AMPK) is involved in skeletal muscle metabolism. Effects of TJ-41 on disuse-induced muscle atrophy are unclear. Methods We subjected differentiated C2C12 myotubes to serum starvation, then examined the effects of TJ-41 on atrogenes expression, AMPK activity and the morphology of the myotubes. Male C57BL/6J mice were subjected to tail-suspension to induce hindlimb atrophy. We administered TJ-41 by gavage to the control group and the tail-suspended group, then examined the effects of TJ-41 on atrogene expression, AMPK activity, and the muscle weight. Results Serum starvation induced the expression of atrogin-1 and MuRF1 in C2C12 myotubes, and TJ-41 significantly downregulated the expression of atrogin-1. Tail-suspension of the mice induced the expression of atrogin-1 and MuRF1 in skeletal muscle as well as its muscle atrophy, whereas TJ-41 treatment significantly downregulated the expression of atrogin-1 and ameliorated the loss of the muscle weight. In addition, TJ-41 also activated AMPK and inactivated Akt and mTOR in skeletal muscle in vivo. Conclusion TJ-41 inhibited atrogenes in an Akt-independent manner as well as activating AMPK in skeletal muscles in vivo, further implying the therapeutic potential of TJ-41 against disuse-induced muscle atrophy and other atrogenes-dependent atrophic conditions.

show abstract

“…Interestingly, the KCa3.1 channel blocker TRAM34 can also increase the level of ROS in endothelial progenitor cells by enhancing NOX activity to increase protein kinase C expression and promote senescence of endothelial progenitor cells [37]. These paradoxical effects of KCa3.1 channel modulators may be due to the different subcellular localization of distribution of KCa3.1 channels in the cell membrane and inner mitochondrial membrane [35].…”

Section: Key Pointsmentioning

confidence: 99%

“…Apart from its role in apoptosis, the mitochondrial KCa3.1 channel has been identified as a novel regulator of oxidative phosphorylation in a pancreatic ductal adenocarcinoma cell line, suggesting that KCa3.1 plays a crucial role in ROS production [34]. Indeed, the mitochondrial KCa3.1 channel is activated by DCEBIO, a pharmacological activator of KCa3.1 in C2C12 mouse myoblasts, which causes depolarization of the mitochondrial membrane potential and leads to an increase in mitochondrial ROS via the activation of Akt/mammalian target of rapamycin (mTOR) pathway [35]. Thus, the mitochondrial KCa3.1 channel has been demonstrated to be a target molecule for DCEBIO-induced muscle hypertrophy [35].…”

Section: Key Pointsmentioning

confidence: 99%

“…Indeed, the mitochondrial KCa3.1 channel is activated by DCEBIO, a pharmacological activator of KCa3.1 in C2C12 mouse myoblasts, which causes depolarization of the mitochondrial membrane potential and leads to an increase in mitochondrial ROS via the activation of Akt/mammalian target of rapamycin (mTOR) pathway [35]. Thus, the mitochondrial KCa3.1 channel has been demonstrated to be a target molecule for DCEBIO-induced muscle hypertrophy [35]. In addition, a study by Ibrahim et al showed that KCa3.1 promotes cell migration and invasion by modulating both calcium and ROS signaling in KRAS-mutated colorectal cancer cells [36].…”

Section: Key Pointsmentioning

confidence: 99%

See 1 more Smart Citation

KCa3.1 in diabetic kidney disease

Huang

Chen²,

Pollock³

2021

Current Opinion in Nephrology &Amp; Hypertension

View full text Add to dashboard Cite

Purpose of reviewDiabetic kidney disease (DKD) is a significant health concern. Innovative strategies to prevent or limit the progression of DKD are urgently needed due to the limitation of existing treatments. KCa3.1, a potassium channel, is involved in a range of biological processes from cell survival to cell death. This review summarizes the current knowledge on the pathophysiological functions of the KCa3.1 channel, specifically its involvement in maintaining mitochondrial function. More specifically, the therapeutic potential of targeting KCa3.1 in DKD is systematically discussed in the review. Recent findingsMitochondrial dysfunction contributes to the development and progression of DKD. Accumulating evidence indicates that KCa3.1 dysregulation plays a crucial role in mitochondrial dysfunction, in addition to driving cellular activation, proliferation and inflammation. Recent studies demonstrate that KCa3.1 deficiency improves diabetes-induced mitochondrial dysfunction in DKD, which is attributed to modulation of mitochondrial quality control through mitigating the altered mitochondrial dynamics and restoring abnormal BNIP3-mediated mitophagy.

show abstract

Opening of Intermediate Conductance Ca²⁺-Activated K⁺ Channels in C2C12 Skeletal Muscle Cells Increases the Myotube Diameter via the Akt/Mammalian Target of Rapamycin Pathway

Cited by 5 publications

References 51 publications

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro

KCa3.1 in diabetic kidney disease

Contact Info

Product

Resources

About

Opening of Intermediate Conductance Ca2+-Activated K+ Channels in C2C12 Skeletal Muscle Cells Increases the Myotube Diameter via the Akt/Mammalian Target of Rapamycin Pathway

Cited by 5 publications

References 51 publications

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Ca2+-Activated K+ Channels in Progenitor Cells of Musculoskeletal Tissues: A Narrative Review

Kampo formula hochu-ekki-to (Bu-Zhong-Yi-Qi-Tang, TJ-41) ameliorates muscle atrophy by modulating atrogenes and AMPK in vivo and in vitro

KCa3.1 in diabetic kidney disease

Contact Info

Product

Resources

About

Opening of Intermediate Conductance Ca²⁺-Activated K⁺ Channels in C2C12 Skeletal Muscle Cells Increases the Myotube Diameter via the Akt/Mammalian Target of Rapamycin Pathway