Direct and indirect activation of the adenosine triphosphate–sensitive potassium channel to induce spinal cord ischemic metabolic tolerance

Ikeno, Yuki; Ghincea, Christian V.; Roda, Gavriel F.; Cheng, Linling; Aftab, Muhammad; Meng, Xianzhong; Weyant, Michael J.; Cleveland, Joseph C.; Fullerton, David A.; Reece, T. Brett

doi:10.1016/j.jtcvs.2021.08.085

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…Diazoxide attenuated spinal cord ischemia-reperfusion injury, and motor function after spinal cord ischemia was improved in a mouse model with diazoxide compared to controls, an action that appeared to be associated with expression of the signaling transducer and activator of transcription (STAT) 3 pathway [150] . These results have been confirmed by several others that have demonstrated the potential of diazoxide to reduce spinal cord injury following ischemia [151][152][153] .…”

Section: The Role Of K Atp Channels In Neuroprotectionsupporting

confidence: 75%

Exploitation of K_ATP channels for cardiac surgery

Bradshaw,

Lawton

2023

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The many ways in which ATP-sensitive potassium (KATP) channels can be exploited for human benefit have expanded over recent decades. Especially since the early 2000s, research has improved our understanding of the components and mechanisms of KATP channels. They have the potential to have a prominent role in cardiac surgery. Pharmacologic and non-pharmacologic activation of KATP channels has been shown to be both cardioprotective and neuroprotective in early basic science and clinical studies. However, many questions remain unanswered and require further study, necessitating further basic science work and large human clinical trials. This review discusses the history and recent progress in the research relating to the use of KATP channels for cardiac surgery.

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Section: The Role Of K Atp Channels In Neuroprotectionsupporting

confidence: 75%

Exploitation of K_ATP channels for cardiac surgery

Bradshaw,

Lawton

2023

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“…Among the ion channels, potassium channels have the most subtypes and the most complex functions and are the focus of much clinical and scientific research. For example, research has been conducted on voltage-gated potassium channels, such as Kv1, Kv2, Kv3, and Kv4 (Heijman et al, 2021 ; Ikeno et al, 2021 ; Kleis et al, 2022 ). The Kv family of potassium channels are glycosylated polypeptide complexes composed of four α-subunits and four β-auxiliaries.…”

Section: Introductionmentioning

confidence: 99%

Rare KCND3 Loss-of-Function Mutation Associated With the SCA19/22

Liu

Hao

et al. 2022

Front. Mol. Neurosci.

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Spinocerebellar ataxia 19/22 (SCA19/22) is a rare neurodegenerative disorder caused by mutations of the KCND3 gene, which encodes the Kv4. 3 protein. Currently, only 22 KCND3 single-nucleotide mutation sites of SCA19/22 have been reported worldwide, and detailed pathogenesis remains unclear. In this study, Sanger sequencing was used to screen 115 probands of cerebellar ataxia families in 67 patients with sporadic cerebellar ataxia and 200 healthy people to identify KCND3 mutations. Mutant gene products showed pathogenicity damage, and the polarity was changed. Next, we established induced pluripotent stem cells (iPSCs) derived from SCA19/22 patients. Using a transcriptome sequencing technique, we found that protein processing in the endoplasmic reticulum was significantly enriched in SCA19/22-iPS-derived neurons and was closely related to endoplasmic reticulum stress (ERS) and apoptosis. In addition, Western blotting of the SCA19/22-iPS-derived neurons showed a reduction in Kv4.3; but, activation of transcription factor 4 (ATF4) and C/EBP homologous protein was increased. Therefore, the c.1130 C>T (p.T377M) mutation of the KCND3 gene may mediate misfold and aggregation of Kv4.3, which activates the ERS and further induces neuron apoptosis involved in SCA19/22.

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