The formation of K V 2.1 macro-clusters is required for sex-specific differences in L-type Ca V 1.2 clustering and function in arterial myocytes.

Autor: Matsumoto C; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., O'Dwyer SC; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Manning D; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Hernandez-Hernandez G; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Rhana P; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Fong Z; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Sato D; Department of Pharmacology, School of Medicine, University of California, Davis, CA, USA., Clancy CE; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Vierra NC; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Trimmer JS; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA., Fernando Santana L; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, CA, USA. lfsantana@ucdavis.edu.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2023 Nov 14; Vol. 6 (1), pp. 1165. Date of Electronic Publication: 2023 Nov 14.
DOI: 10.1038/s42003-023-05527-1
Abstrakt: In arterial myocytes, the canonical function of voltage-gated Ca V 1.2 and K V 2.1 channels is to induce myocyte contraction and relaxation through their responses to membrane depolarization, respectively. Paradoxically, K V 2.1 also plays a sex-specific role by promoting the clustering and activity of Ca V 1.2 channels. However, the impact of K V 2.1 protein organization on Ca V 1.2 function remains poorly understood. We discovered that K V 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 V 2.1 channels seems unrelated to density or macro-clustering in arterial myocytes. Disrupting the K V 2.1 clustering site (K V 2.1 S590A ) eliminated K V 2.1 macro-clustering and sex-specific differences in Ca V 1.2 cluster size and activity. We propose that the degree of K V 2.1 clustering tunes Ca V 1.2 channel function in a sex-specific manner in arterial myocytes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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