ArticleCirculation research2008
IP3 constricts cerebral arteries via IP3 receptor-mediated TRPC3 channel activation and independently of sarcoplasmic reticulum Ca2+ release.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
73 citing papers in PubMed, 111 citations in OpenAlex.
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- The nonexcitable smooth muscle: remodeling the smooth muscle ion transport toolkit in disease.Physiological reviews · 2026Review
- A pericyte chloride clamp mechanism governs capillary control of cerebral blood flow.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The role of IPPflugers Archiv : European journal of physiology · 2026Review
- Cerebral capillary computation.American journal of physiology. Cell physiology · 2026Review
- Non-Ser36 phosphorylated p66Shc inhibits TRPC-dependent and TRPC-independent calcium influx in vascular smooth muscle cells.Biochemical and biophysical research communications · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Docosahexaenoic acid protects against alcohol-induced constriction of cerebral arteries and inhibition of vascular smooth muscle BK channels.Alcohol, clinical & experimental research · 2025Article
- Increased luminal pressure in brain capillaries drives TRPC3-dependent depolarization and constriction of transitional pericytes.Science signaling · 2025Article
- Role of transient receptor potential channels in the regulation of vascular tone.Drug discovery today · 2024Review
- Electro-metabolic signaling.The Journal of general physiology · 2024Article
- Progesterone activation of βNature communications · 2023Article
- Vascular mechanotransduction.Physiological reviews · 2023Review
- Mechanisms and physiological implications of cooperative gating of clustered ion channels.Physiological reviews · 2022Review
- Inhibition of TRPC3 channels by a novel pyrazole compound confers antiseizure effects.Epilepsia · 2022Article
- STIMulating blood pressure.eLife · 2022Article
- IP3 receptor orchestrates maladaptive vascular responses in heart failure.The Journal of clinical investigation · 2022Article
- Ion channel molecular complexes in vascular smooth muscle.Frontiers in physiology · 2022Review
- TRPC6, a therapeutic target for pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Role of TRP ion channels in cerebral circulation and neurovascular communication.Neuroscience letters · 2021Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Vasoconstrictors that bind to phospholipase C-coupled receptors elevate inositol-1,4,5-trisphosphate (IP(3)). IP(3) is generally considered to elevate intracellular Ca(2+) concentration ([Ca(2+)](i)) in arterial myocytes and induce vasoconstriction via a single mechanism: by activating sarcoplasmic reticulum (SR)-localized IP(3) receptors, leading to intracellular Ca(2+) release. We show that IP(3) also stimulates vasoconstriction via a SR Ca(2+) release-independent mechanism. In isolated cerebral artery myocytes and arteries in which SR Ca(2+) was depleted to abolish Ca(2+) release (measured using D1ER, a fluorescence resonance energy transfer-based SR Ca(2+) indicator), IP(3) activated 15 pS sarcolemmal cation channels, generated a whole-cell cation current (I(Cat)) caused by Na(+) influx, induced membrane depolarization, elevated [Ca(2+)](i), and stimulated vasoconstriction. The IP(3)-induced I(Cat) and [Ca(2+)](i) elevation were attenuated by cation channel (Gd(3+), 2-APB) and IP(3) receptor (xestospongin C, heparin, 2-APB) blockers. TRPC3 (canonical transient receptor potential 3) channel knockdown with short hairpin RNA and diltiazem and nimodipine, voltage-dependent Ca(2+) channel blockers, reduced the SR Ca(2+) release-independent, IP(3)-induced [Ca(2+)](i) elevation and vasoconstriction. In pressurized arteries, SR Ca(2+) depletion did not alter IP(3)-induced constriction at 20 mm Hg but reduced IP(3)-induced constriction by approximately 39% at 60 mm Hg. [Ca(2+)](i) elevations and constrictions induced by endothelin-1, a phospholipase C-coupled receptor agonist, were both attenuated by TRPC3 knockdown and xestospongin C in SR Ca(2+)-depleted arteries. In summary, we describe a novel mechanism of IP(3)-induced vasoconstriction that does not occur as a result of SR Ca(2+) release but because of IP(3) receptor-dependent I(Cat) activation that requires TRPC3 channels. The resulting membrane depolarization activates voltage-dependent Ca(2+) channels, leading to a myocyte [Ca(2+)](i) elevation, and vasoconstriction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.