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KCNJ8/ABCC9-contain...
KCNJ8/ABCC9-containing K-ATP channel modulates brain vascular smooth muscle development and neurovascular coupling
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- Ando, Koji (author)
- Uppsala universitet,Vaskulärbiologi,Nippon Med Sch, Inst Adv Med Sci, Dept Mol Pathophysiol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan.;Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Regenerat Med & Tissue Engn, 6-1 Kishibe Shinmachi, Suita, Osaka 5648565, Japan.
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- Tong, Lei (author)
- Yale Sch Med, Dept Neurol, New Haven, CT USA.
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- Peng, Di (author)
- Uppsala universitet,Vaskulärbiologi
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- Vazquez-Liebanas, Elisa (author)
- Uppsala universitet,Vaskulärbiologi
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- Chiyoda, Hirohisa (author)
- Nippon Med Sch, Inst Adv Med Sci, Dept Mol Pathophysiol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan.;Natl Cerebral & Cardiovasc Ctr Res Inst, Dept Regenerat Med & Tissue Engn, 6-1 Kishibe Shinmachi, Suita, Osaka 5648565, Japan.
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- He, Liqun (author)
- Uppsala universitet,Vaskulärbiologi
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- Liu, Jianping (author)
- Karolinska Institutet
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- Kawakami, Koichi (author)
- Natl Inst Genet, Lab Mol & Dev Biol, 1111 Yata, Mishima, Shizuoka 4118540, Japan.;SOKENDAI Grad Univ Adv Studies, Dept Genet, 1111 Yata, Mishima, Shizuoka 4118540, Japan.
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- Mochizuki, Naoki (author)
- Natl Cerebral & Cardiovasc Ctr, Dept Cell Biol, Res Inst, 6-1 Kishibe Shinmachi, Suita, Osaka 5648565, Japan.
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- Fukuhara, Shigetomo (author)
- Nippon Med Sch, Inst Adv Med Sci, Dept Mol Pathophysiol, Bunkyo Ku, 1-1-5 Sendagi, Tokyo 1138602, Japan.
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- Grutzendler, Jaime (author)
- Yale Sch Med, Dept Neurol, New Haven, CT USA.
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- Betsholtz, Christer (author)
- Uppsala universitet,Vaskulärbiologi,Karolinska Inst, Dept Med Huddinge MedH, Campus Flemingsburg,Blickagangen 16, S-14157 Huddinge, Sweden.
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(creator_code:org_t)
- Elsevier, 2022
- 2022
- English.
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In: Developmental Cell. - : Elsevier. - 1534-5807 .- 1878-1551. ; 57:11, s. 1383-1399.e7
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Loss- or gain-of-function mutations in ATP-sensitive potassium channel (K-ATP)-encoding genes, KCNJ8 and ABCC9, cause human central nervous system disorders with unknown pathogenesis. Here, using mice, zebrafish, and cell culture models, we investigated cellular and molecular causes of brain dysfunctions derived from altered K-ATP channel function. We show that genetic/chemical inhibition or activation of KCNJ8/ABCC9-containing K-ATP channel function leads to brain-selective suppression or promotion of arterial/arteriolar vascular smooth muscle cell (VSMC) differentiation, respectively. We further show that brain VSMCs develop from KCNJ8/ABCC9-containing K-ATP channel-expressing mural cell progenitor and that K-ATP channel cell autonomously regulates VSMC differentiation through modulation of intracellular Ca2+ oscillation via voltage-dependent calcium channels. Consistent with defective VSMC development, Kcnj8 knockout mice showed deficiency in vasoconstrictive capacity and neuronal-evoked vasodilation leading to local hyperemia. Our results demonstrate a role for KCNJ8/ABCC9-containing K-ATP channels in the differentiation of brain VSMC, which in turn is necessary for fine-tuning of cerebral blood flow.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Ando, Koji
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Tong, Lei
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Peng, Di
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Vazquez-Liebanas ...
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Chiyoda, Hirohis ...
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He, Liqun
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show more...
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Liu, Jianping
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Kawakami, Koichi
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Mochizuki, Naoki
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Fukuhara, Shiget ...
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Grutzendler, Jai ...
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Betsholtz, Chris ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Developmental Ce ...
- By the university
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Uppsala University
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Karolinska Institutet