ArticleCirculation research2014
Protein kinase A-phosphorylated KV1 channels in PSD95 signaling complex contribute to the resting membrane potential and diameter of cerebral arteries.
Article in Circulation research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
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- Synaptic-like transmission between neural axons and arteriolar smooth muscle cells drives cerebral neurovascular coupling.Nature neuroscience · 2024Article
- Mechanisms of Vascular CaHandbook of experimental pharmacology · 2023Article
- Ion channel molecular complexes in vascular smooth muscle.Frontiers in physiology · 2022Review
- Metoprolol ImpairsThe Journal of pharmacology and experimental therapeutics · 2021Article
- Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle.Cellular and molecular life sciences : CMLS · 2021Review
- AKAP5 complex facilitates purinergic modulation of vascular L-type CaNature communications · 2020Article
- βAnnual review of pharmacology and toxicology · 2020Review
- A GeLife · 2019Article
- Molecular determinants of beta-adrenergic signaling to voltage-gated KMicrocirculation (New York, N.Y. : 1994) · 2018Review
- KMicrocirculation (New York, N.Y. : 1994) · 2018Review
- KMicrocirculation (New York, N.Y. : 1994) · 2018Review
- Dynamic Regulation of the Subunit Composition of BK Channels in Smooth Muscle.Circulation research · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Ser1928 phosphorylation by PKA stimulates the L-type Ca2+ channel CaV1.2 and vasoconstriction during acute hyperglycemia and diabetes.Science signaling · 2017Article
- Potassium Channels in Regulation of Vascular Smooth Muscle Contraction and Growth.Advances in pharmacology (San Diego, Calif.) · 2017Review
- Beta1-adrenergic receptor-mediated dilation of rat cerebral artery requires Shaker-type KV1 channels on PSD95 scaffold.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2015Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationalePostsynaptic density-95 (PSD95) is a scaffolding protein that associates with voltage-gated, Shaker-type K(+) (KV1) channels and promotes the expression of KV1 channels in vascular smooth muscle cells of the cerebral (cVSMCs) circulation. However, the physiological role of PSD95 in mediating molecular signaling in cVSMCs is unknown.
objectiveWe explored whether a specific interaction between PSD95 and KV1 channels enables protein kinase A phosphorylation of KV1 channels in cVSMCs to promote vasodilation. METHODS AND
resultsRat cerebral arteries were used for analyses. A membrane-permeable peptide (KV1-C peptide) corresponding to the postsynaptic density-95, discs large, zonula occludens-1 binding motif in the C terminus of KV1.2α was designed as a dominant-negative peptide to disrupt the association of KV1 channels with PSD95. Application of KV1-C peptide to cannulated, pressurized cerebral arteries rapidly induced vasoconstriction and depolarized cVSMCs. These events corresponded to reduced coimmunoprecipitation of the PSD95 and KV1 proteins without altering surface expression. Middle cerebral arterioles imaged in situ through cranial window also constricted rapidly in response to local application of KV1-C peptide. Patch-clamp recordings confirmed that KV1-C peptide attenuates KV1 channel blocker (5-(4-phenylalkoxypsoralen))-sensitive current in cVSMCs. Western blots using a phospho-protein kinase A substrate antibody revealed that cerebral arteries exposed to KV1-C peptide showed markedly less phosphorylation of KV1.2α subunits. Finally, phosphatase inhibitors blunted both KV1-C peptide-mediated and protein kinase A inhibitor peptide-mediated vasoconstriction.
conclusionsThese findings provide initial evidence that protein kinase A phosphorylation of KV1 channels is enabled by a dynamic association with PSD95 in cerebral arteries and suggest that a disruption of such association may compromise cerebral vasodilation and blood flow.
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