ArticleJournal of molecular neuroscience : MN2014
Pituitary adenylate cyclase activating polypeptide (PACAP) dilates cerebellar arteries through activation of large-conductance Ca(2+)-activated (BK) and ATP-sensitive (K ATP) K (+) channels.
Article in Journal of molecular neuroscience : MN, 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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The trial behind it
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- PACAP38-induced migraine attacks are independent of CGRP signaling: a randomized controlled trial.The journal of headache and pain · 2025Trial
- Hypersensitivity to PACAP-38 in post-traumatic headache: a randomized clinical trial.Brain : a journal of neurology · 2024Trial
- Potassium channels in vascular smooth muscle cells.Physiological reviews · 2026Review
- Ion Channel Disturbances in Migraine Headache: Exploring the Potential Role of the Kynurenine System in the Context of the Trigeminovascular System.International journal of molecular sciences · 2023Review
- Future targets for migraine treatment beyond CGRP.The journal of headache and pain · 2023Review
- Involvement of Potassium Channel Signalling in Migraine Pathophysiology.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Novel Therapeutic Targets for Migraine.Biomedicines · 2023Review
- Increased pituitary adenylate cyclase-activating peptide genes expression in the prefrontal cortex in schizophrenia in relation to suicide.Frontiers in molecular neuroscience · 2023Article
- The role of high-conductance calcium-activated potassium channel in headache and migraine pathophysiology.Basic & clinical pharmacology & toxicology · 2022Review
- Pituitary Adenylate Cyclase Activating Polypeptide Inhibits ANeuroscience · 2021Article
- Adaptive Changes in the Central Control of Energy Homeostasis Occur in Response to Variations in Energy Status.International journal of molecular sciences · 2021Review
- Targeting BKCNS drugs · 2020Review
- The Ion Channel and GPCR Toolkit of Brain Capillary Pericytes.Frontiers in cellular neuroscience · 2020Review
- Parallel signaling pathways of pituitary adenylate cyclase activating polypeptide (PACAP) regulate several intrinsic ion channels.Annals of the New York Academy of Sciences · 2019Review
- Article
- Dihydromyricetin improves vascular hyporesponsiveness in experimental sepsis via attenuating the over-excited MaxiK and KPharmaceutical biology · 2018Article
- Calcium- and voltage-gated BK channels in vascular smooth muscle.Pflugers Archiv : European journal of physiology · 2018Review
- Genetic Insights into Cerebrovascular Disorders: A Comprehensive Review.Journal of vascular and interventional neurology · 2017Article
- Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles.Comprehensive Physiology · 2017Review
- Proteomic differences in brain vessels of Alzheimer's disease mice: Normalization by PPARγ agonist pioglitazone.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pituitary adenylate cyclase activating polypeptide (PACAP) is a potent vasodilator of numerous vascular beds, including cerebral arteries. Although PACAP-induced cerebral artery dilation is suggested to be cyclic AMP (cAMP)-dependent, the downstream intracellular signaling pathways are still not fully understood. In this study, we examined the role of smooth muscle K(+) channels and hypothesized that PACAP-mediated increases in cAMP levels and protein kinase A (PKA) activity result in the coordinate activation of ATP-sensitive K(+) (KATP) and large-conductance Ca(2+)-activated K(+) (BK) channels for cerebral artery dilation. Using patch-clamp electrophysiology, we observed that PACAP enhanced whole-cell KATP channel activity and transient BK channel currents in freshly isolated rat cerebellar artery myocytes. The increased frequency of transient BK currents following PACAP treatment is indicative of increased intracellular Ca(2+) release events termed Ca(2+) sparks. Consistent with the electrophysiology data, the PACAP-induced vasodilations of cannulated cerebellar artery preparations were attenuated by approximately 50 % in the presence of glibenclamide (a KATP channel blocker) or paxilline (a BK channel blocker). Further, in the presence of both blockers, PACAP failed to cause vasodilation. In conclusion, our results indicate that PACAP causes cerebellar artery dilation through two mechanisms: (1) KATP channel activation and (2) enhanced BK channel activity, likely through increased Ca(2+) spark frequency.
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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.