据报道，K 通道功能的改变，例如电压和 Ca2 激活的大电导 K 通道 (BKCa)，可促进乳腺癌 (BC) 的发生和进展。然而，潜在的分子机制仍然难以捉摸。在这里，我们提供了位于小鼠和人类 BC 细胞线粒体内膜 (mitoBKCa) 的 BKCa 剪接变体的电生理学证据。通过基因敲低和基因敲除与细胞渗透性 BKCa 通道阻滞剂相结合，我们发现 mitoBKCa 调节整体细胞和线粒体能量产生，并介导被称为“Warburg 效应”的代谢重新布线，从而促进 BC 细胞增殖。氧气的存在和不存在。此外，我们在临床 BC 样本中分别检测到低丰度或高丰度的 mitoBKCa 和 BKCa 转录本。总之，我们的结果强调，靶向 mitoBKCa 可能代表未来选定的 BC 患者的治疗策略。© 2023，Bischof 等人。

Alterations in the function of K+ channels such as the voltage- and Ca2+-activated K+ channel of large conductance (BKCa) reportedly promote breast cancer (BC) development and progression. Underlying molecular mechanisms remain, however, elusive. Here, we provide electrophysiological evidence for a BKCa splice variant localized to the inner mitochondrial membrane of murine and human BC cells (mitoBKCa). Through a combination of genetic knockdown and knockout along with a cell permeable BKCa channel blocker, we show that mitoBKCa modulates overall cellular and mitochondrial energy production, and mediates the metabolic rewiring referred to as the 'Warburg effect', thereby promoting BC cell proliferation in the presence and absence of oxygen. Additionally, we detect mitoBKCa and BKCa transcripts in low or high abundance, respectively, in clinical BC specimens. Together, our results emphasize, that targeting mitoBKCa could represent a treatment strategy for selected BC patients in future.© 2023, Bischof et al.