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Uncovering the K IR Mechanosignaling Complex in Vascular Smooth Muscle
Author(s) -
Fletcher Jacob,
Welsh Donald
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02802
Subject(s) - mechanosensitive channels , microbiology and biotechnology , cytochalasin d , cytoskeleton , vascular smooth muscle , context (archaeology) , ion channel , myocyte , chemistry , scaffold protein , actin , patch clamp , actin cytoskeleton , biology , neuroscience , electrophysiology , signal transduction , biochemistry , endocrinology , cell , receptor , paleontology , smooth muscle
Inwardly rectifying potassium (K IR ) channels contribute to the setting of membrane potential in vascular smooth muscle (VSM). Recent work has demonstrated their regulation by pressure, although the underlying mechanism remains unclear. This study sought to identify key signaling components that enable this mechanosensitive response in rat cerebral arterial myocytes. Initial patch clamp electrophysiology confirmed that pressure, initiated by a hyposmotic challenge, suppresses K IR currents in isolated cells. Actin disruption with Cytochalasin D and Latrunculin A abolished this response, implying participation of the cytoskeleton. Interactions between ion channels and actin filaments are often facilitated through structural protein intermediates. In this context, we examined syntrophin and caveolin‐1 scaffolding proteins as they have each been previously found to interact with K IR channels. Peptide blockade of caveolin‐1 prevented K IR suppression after hyposmotic challenge in subsequent patch clamp experiments. Immunohistochemistry highlighted expression of both syntrophin and caveolin‐1 in VSM, while proximity ligation assay revealed their co‐localization with K IR 2.2 subunits. These findings provide evidence that K IR mechanosensitivity involves interactions with the cytoskeleton which are likely mediated by scaffolding proteins.