Ryanodine Receptors in Muscarinic Receptor-mediated Bronchoconstriction

Ryanodine receptors (RyRs), intracellular calcium release channels essential for skeletal and cardiac muscle contraction, are also expressed in various types of smooth muscle cells. In particular, recent studies have suggested that in airway smooth muscle cells (ASMCs) provoked by spasmogens, stored...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2005-07, Vol.280 (28), p.26287-26294
Main Authors: Du, Wanglei, Stiber, Jonathan A., Rosenberg, Paul B., Meissner, Gerhard, Eu, Jerry P.
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
Bronchi - metabolism
Bronchi - pathology
Bronchi - physiology
Calcium - metabolism
Carbachol - metabolism
Carbachol - pharmacology
Cell Membrane - metabolism
Cell Nucleus - metabolism
Cholinergic Agonists - pharmacology
Dantrolene - pharmacology
Dose-Response Relationship, Drug
Immunoblotting
Male
Mice
Mice, Inbred C57BL
Microscopy, Confocal
Microscopy, Fluorescence
Models, Biological
Muscle Contraction
Muscle Relaxants, Central - pharmacology
Muscle, Skeletal - metabolism
Muscle, Smooth - drug effects
Muscle, Smooth - metabolism
Protein Isoforms
Receptors, Muscarinic - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Ryanodine - pharmacology
Ryanodine Receptor Calcium Release Channel - biosynthesis
Ryanodine Receptor Calcium Release Channel - chemistry
Ryanodine Receptor Calcium Release Channel - metabolism
Signal Transduction
Tissue Distribution
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Ryanodine receptors (RyRs), intracellular calcium release channels essential for skeletal and cardiac muscle contraction, are also expressed in various types of smooth muscle cells. In particular, recent studies have suggested that in airway smooth muscle cells (ASMCs) provoked by spasmogens, stored calcium release by the cardiac isoform of RyR (RyR2) contributes to the calcium response that leads to airway constriction (bronchoconstriction). Here we report that mouse ASMCs also express the skeletal muscle and brain isoforms of RyRs (RyR1 and RyR3, respectively). In these cells, RyR1 is localized to the periphery near the cell membrane, whereas RyR3 is more centrally localized. Moreover, RyR1 and/or RyR3 in mouse airway smooth muscle also appear to mediate bronchoconstriction caused by the muscarinic receptor agonist carbachol. Inhibiting all RyR isoforms with ≥200 μm ryanodine attenuated the graded carbachol-induced contractile responses of mouse bronchial rings and calcium responses of ASMCs throughout the range of carbachol used (50 nm to ≥3 μm). In contrast, inhibiting only RyR1 and RyR3 with 25 μm dantrolene attenuated these responses caused by high (>500 nm) but not by low concentrations of carbachol. These data suggest that, as the stimulation of muscarinic receptor in the airway smooth muscle increases, RyR1 and/or RyR3 also mediate the calcium response and thus bronchoconstriction. Our findings provide new insights into the complex calcium signaling in ASMCs and suggest that RyRs are potential therapeutic targets in bronchospastic disorders such as asthma.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M502905200