Dust from hog confinement facilities impairs Ca2+ mobilization from sarco(endo)plasmic reticulum by inhibiting ryanodine receptors

Chengju Tian, Caronda J. Moore, Puttappa Dodmane, Chun Hong Shao, Debra Romberger, Myron Lee Toews, Keshore R Bidasee

Research output: Contribution to journalArticle

Abstract

Individuals working in commercial hog confinement facilities have elevated incidences of headaches, depression, nausea, skeletal muscle weakness, fatigue, gastrointestinal disorders, and cardiovascular diseases, and the molecular mechanisms for these nonrespiratory ailments remain incompletely undefined. A common element underlying these diverse pathophysiologies is perturbation of intracellular Ca2+ homeostasis. This study assessed whether the dust generated inside hog confinement facilities contains compounds that alter Ca2+ mobilization via ryanodine receptors (RyRs), key intracellular channels responsible for mobilizing Ca2+ from internal stores to elicit an array of physiologic functions. Hog barn dust (HBD) was extracted with phosphate-buffered saline, sterile-filtered (0.22 μm), and sizeseparated using Sephadex G-100 resin. Fractions (F) 1 through 9 (Mw >10,000 Da) had no measurable effects on RyR isoforms. However, F10 through F17, which contained compounds of Mw ≤2,000 Da, modulated the [3H]ryanodine binding to RyR1, RyR2, and RyR3 in a biphasic (Gaussian) manner. The Ki values for F13, the most potent fraction, were 3.8 ± 0.2 μg/ml for RyR1, 0.2 ± 0.01 μg/ml and 19.1 ± 2.8 μg/ml for RyR2 (two binding sites), and 44.9 ± 2.8 μg/ml and 501.6 ± 9.2 μg/ml for RyR3 (two binding sites). In lipid bilayer assays, F13 dose-dependently decreased the open probabilities of RyR1, RyR2, and RyR3. Pretreating differentiated mouse skeletal myotubes (C2C12 cells) with F13 blunted the amplitudes of ryanodine- and K +-induced Ca2+ transients. Because RyRs are present in many cell types, impairment in Ca2+ mobilization from internal stores via these channels is a possible mechanism by which HBD may trigger these seemingly unrelated pathophysiologies.

Original languageEnglish (US)
Pages (from-to)665-674
Number of pages10
JournalJournal of Applied Physiology
Volume114
Issue number5
DOIs
StatePublished - Mar 1 2013

Fingerprint

Reticulum
Ryanodine Receptor Calcium Release Channel
Dust
Ryanodine
Binding Sites
Muscle Fatigue
Gastrointestinal Diseases
Skeletal Muscle Fibers
Muscle Weakness
Lipid Bilayers
Nausea
Headache
Protein Isoforms
Skeletal Muscle
Homeostasis
Cardiovascular Diseases
Phosphates

Keywords

  • Cardiovascular diseases and nonrespiratory ailments
  • Intracellular Ca homeostasis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Dust from hog confinement facilities impairs Ca2+ mobilization from sarco(endo)plasmic reticulum by inhibiting ryanodine receptors. / Tian, Chengju; Moore, Caronda J.; Dodmane, Puttappa; Shao, Chun Hong; Romberger, Debra; Toews, Myron Lee; Bidasee, Keshore R.

In: Journal of Applied Physiology, Vol. 114, No. 5, 01.03.2013, p. 665-674.

Research output: Contribution to journalArticle

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