Apelin-13 inhibits large-conductance Ca2+-activated K+ channels in cerebral artery smooth muscle cells via a PI3-kinase dependent mechanism

Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM) cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+)-activated K(+) (BKCa) channels in VSM cells are critical regulators of memb...

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Bibliographic Details
Published in:PloS one 2013-12, Vol.8 (12), p.e83051-e83051
Main Authors: Modgil, Amit, Guo, Lirong, O'Rourke, Stephen T, Sun, Chengwen
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 3-kinase
AKT protein
Animals
Apelin
Arteries
Calcium channels
Calcium conductance
Calcium Signaling - drug effects
Cardiomyocytes
Cardiovascular system
Cerebral Arteries - cytology
Cerebral Arteries - drug effects
Channel gating
Channel opening
Channels
Conductance
Current density
Data processing
Endothelium
Enzyme inhibitors
Immunoglobulins
Intercellular Signaling Peptides and Proteins - pharmacology
Intercellular Signaling Peptides and Proteins - physiology
Kinases
Ligands
Male
Membrane potential
Membranes
Muscle, Smooth, Vascular - drug effects
Muscles
Nitric oxide
Patch-Clamp Techniques
Patches (structures)
Pertussis Toxin - pharmacology
Pharmaceutical sciences
Phosphatidylinositol 3-Kinase - physiology
Potassium
Potassium channels (calcium-gated)
Potassium Channels, Calcium-Activated - antagonists & inhibitors
Potassium conductance
Pretreatment
Proteins
Rats
Rats, Sprague-Dawley
Receptors
Regulation
Resistance
Rodents
Signal transduction
Signaling
Smooth muscle
Vasoconstriction
Veins & arteries
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Summary:Apelin-13 causes vasoconstriction by acting directly on APJ receptors in vascular smooth muscle (VSM) cells; however, the ionic mechanisms underlying this action at the cellular level remain unclear. Large-conductance Ca(2+)-activated K(+) (BKCa) channels in VSM cells are critical regulators of membrane potential and vascular tone. In the present study, we examined the effect of apelin-13 on BK(Ca) channel activity in VSM cells, freshly isolated from rat middle cerebral arteries. In whole-cell patch clamp mode, apelin-13 (0.001-1 μM) caused concentration-dependent inhibition of BK(Ca) in VSM cells. Apelin-13 (0.1 µM) significantly decreased BK(Ca) current density from 71.25 ± 8.14 pA/pF to 44.52 ± 7.10 pA/pF (n=14 cells, P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0083051