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The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
by
Clancy, Colleen E.
, Fernando Santana, L.
, Sato, Daisuke
, O’Dwyer, Samantha C.
, Vierra, Nicholas C.
, Manning, Declan
, Rhana, Paula
, Trimmer, James S.
, Fong, Zhihui
, Hernandez-Hernandez, Gonzalo
, Matsumoto, Collin
in
14
/ 14/1
/ 14/19
/ 14/35
/ 631/443/592
/ 692/4019/592
/ 9/74
/ Biology
/ Biomedical and Life Sciences
/ Calcium channels (voltage-gated)
/ Channel gating
/ Depolarization
/ Dihydropyridine
/ Electrophysiology
/ Life Sciences
/ Membrane potential
/ Myocytes
/ Phosphorylation
/ Potassium channels (voltage-gated)
/ Sex
/ Smooth muscle
2023
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The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
by
Clancy, Colleen E.
, Fernando Santana, L.
, Sato, Daisuke
, O’Dwyer, Samantha C.
, Vierra, Nicholas C.
, Manning, Declan
, Rhana, Paula
, Trimmer, James S.
, Fong, Zhihui
, Hernandez-Hernandez, Gonzalo
, Matsumoto, Collin
in
14
/ 14/1
/ 14/19
/ 14/35
/ 631/443/592
/ 692/4019/592
/ 9/74
/ Biology
/ Biomedical and Life Sciences
/ Calcium channels (voltage-gated)
/ Channel gating
/ Depolarization
/ Dihydropyridine
/ Electrophysiology
/ Life Sciences
/ Membrane potential
/ Myocytes
/ Phosphorylation
/ Potassium channels (voltage-gated)
/ Sex
/ Smooth muscle
2023
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The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
by
Clancy, Colleen E.
, Fernando Santana, L.
, Sato, Daisuke
, O’Dwyer, Samantha C.
, Vierra, Nicholas C.
, Manning, Declan
, Rhana, Paula
, Trimmer, James S.
, Fong, Zhihui
, Hernandez-Hernandez, Gonzalo
, Matsumoto, Collin
in
14
/ 14/1
/ 14/19
/ 14/35
/ 631/443/592
/ 692/4019/592
/ 9/74
/ Biology
/ Biomedical and Life Sciences
/ Calcium channels (voltage-gated)
/ Channel gating
/ Depolarization
/ Dihydropyridine
/ Electrophysiology
/ Life Sciences
/ Membrane potential
/ Myocytes
/ Phosphorylation
/ Potassium channels (voltage-gated)
/ Sex
/ Smooth muscle
2023
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The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
Journal Article
The formation of KV2.1 macro-clusters is required for sex-specific differences in L-type CaV1.2 clustering and function in arterial myocytes
2023
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Overview
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.
Advanced imaging and electrophysiology show that phosphorylation boosts the size of K
V
2.1 clusters, which in turn modulates dihydropyridine-sensitive Ca
V
1.2 channel organization and function in arterial smooth muscle, with variations based on sex.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
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