Lack of activity of the mitochondrial large-conductance calcium-regulated potassium channels in senescent vascular smooth muscle cells.

IF 5.3 3区医学 Q2 CELL BIOLOGY Mechanisms of Ageing and Development Pub Date : 2023-10-01 DOI:10.1016/j.mad.2023.111871

Agata Głuchowska , Barbara Kalenik , Bogusz Kulawiak , Antoni Wrzosek , Adam Szewczyk , Piotr Bednarczyk , Grażyna Mosieniak

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Abstract

A limited number of studies have shown functional changes in mitochondrial ion channels in aging and senescent cells. We have identified, for the first time, mitochondrial large-conductance calcium-regulated potassium channels in human smooth muscle mitochondria. This channel, with a conductance of 273 pS, was regulated by calcium ions and membrane potential. Additionally, it was activated by the potassium channel opener NS11021 and blocked by paxilline. Importantly, we have shown that senescence of these cells induced by hydrogen peroxide treatment leads to the disappearance of potassium channel protein levels and channel activity measured by the single channel patch-clamp technique. Our data suggest that disturbances in the expression of mitochondrial large conductance calcium-regulated potassium channels may be hallmarks of cellular senescence and contribute to the misregulation of mitochondrial function in senescent cells.

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衰老血管平滑肌细胞线粒体大电导钙调节钾通道缺乏活性。

数量有限的研究表明，衰老和衰老细胞中线粒体离子通道的功能变化。我们首次在人类平滑肌线粒体中发现了线粒体大电导钙调节钾通道。该通道的电导率为273pS，受钙离子和膜电位的调节。此外，它被钾通道开放剂NS11021激活，并被帕罗西汀阻断。重要的是，我们已经表明，过氧化氢处理诱导的这些细胞衰老会导致钾通道蛋白水平和单通道膜片钳技术测量的通道活性的消失。我们的数据表明，线粒体大电导钙调节钾通道表达的紊乱可能是细胞衰老的标志，并导致衰老细胞线粒体功能的失调。

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来源期刊

Mechanisms of Ageing and Development 医学-老年医学

CiteScore

11.10

自引率

1.90%

发文量

审稿时长

32 days

期刊介绍： Mechanisms of Ageing and Development is a multidisciplinary journal aimed at revealing the molecular, biochemical and biological mechanisms that underlie the processes of aging and development in various species as well as of age-associated diseases. Emphasis is placed on investigations that delineate the contribution of macromolecular damage and cytotoxicity, genetic programs, epigenetics and genetic instability, mitochondrial function, alterations of metabolism and innovative anti-aging approaches. For all of the mentioned studies it is necessary to address the underlying mechanisms. Mechanisms of Ageing and Development publishes original research, review and mini-review articles. The journal also publishes Special Issues that focus on emerging research areas. Special issues may include all types of articles following peered review. Proposals should be sent directly to the Editor-in-Chief.