Matsumoto Collin, O'Dwyer Samantha C, Manning Declan, Hernandez-Hernandez Gonzalo, Rhana Paula, Fong Zhihui, Sato Daisuke, Clancy Colleen E, Vierra Nicholas C, Trimmer James S, Santana L Fernando
bioRxiv. 2023 Jun 29:2023.06.27.546725. doi: 10.1101/2023.06.27.546725.
In arterial myocytes, the canonical function of voltage-gated Ca 1.2 and K 2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, K 2.1 also plays a sex-specific role by promoting the clustering and activity of Ca 1.2 channels. However, the impact of K 2.1 protein organization on Ca 1.2 function remains poorly understood. We discovered that K 2.1 forms micro-clusters, which can transform into large macro-clusters when a critical clustering site (S590) in the channel is phosphorylated in arterial myocytes. Notably, female myocytes exhibit greater phosphorylation of S590, and macro-cluster formation compared to males. Contrary to current models, the activity of K 2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the K 2.1 clustering site (K 2.1 ) eliminated K 2.1 macro-clustering and sex-specific differences in Ca 1.2 cluster size and activity. We propose that the degree of K 2.1 clustering tunes Ca 1.2 channel function in a sex-specific manner in arterial myocytes.
在动脉肌细胞中，电压门控Ca 1.2和K 2.1通道的经典功能分别是通过对膜去极化的反应来诱导肌细胞收缩和舒张。矛盾的是，K 2.1还通过促进Ca 1.2通道的聚集和活性发挥性别特异性作用。然而，K 2.1蛋白组织对Ca 1.2功能的影响仍知之甚少。我们发现K 2.1形成微簇，当通道中的关键聚集位点（S590）在动脉肌细胞中被磷酸化时，微簇可转变为大的宏簇。值得注意的是，与雄性相比，雌性肌细胞中S590的磷酸化程度更高，且宏簇形成更多。与当前模型相反，K 2.1通道的活性似乎与动脉肌细胞中的密度或宏簇形成无关。破坏K 2.1聚集位点（K 2.1 ）消除了K 2.1宏簇形成以及Ca 1.2簇大小和活性的性别特异性差异。我们提出，K 2.1聚集程度以性别特异性方式调节动脉肌细胞中Ca 1.2通道的功能。
