Divergent Mechanisms Leading to Signaling Dysfunction in Embryonic Muscle by Bisphenol A and Tetrabromobisphenol A

Rui Zhang, Isaac N Pessah

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Bisphenol A (BPA) and its brominated derivative tetrabromobisphenol A (TBBPA) are high production volume chemicals used in the manufacture of various consumer products. Although regarded as endocrine disruptors, these chemicals are suspected to exert nongenomic actions on muscle function that are not well understood. Using skeletal muscle microsomes, we examined the effects of BPA and TBBPA on ryanodine receptor type 1 (RyR1), dihydropyridine receptor (DHPR), and sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA). We assessed the impact of these chemicals on Ca2+ dynamics and signaling in embryonic skeletal myotubes through fluorescent Ca2+ imaging and measurement of resting membrane potential (Vm). TBBPA activated RyR1 and inhibited DHPR and SERCA, inducing a net efflux of Ca2+ from loaded microsomes, whereas BPA exhibited little or no activity at these targets. Regardless, both compounds disrupted the function of intact myotubes. TBBPA diminished and eventually abrogated Ca2+ transients, altered intracellular Ca2+ equilibrium, and caused Vm depolarization. For some cells, BPA caused rapid Ca2+ transient loss without marked changes in cytosolic and sarcoplasmic reticulum Ca2+ levels, likely owing to altered cellular excitability as a result of BPA-induced Vm hyperpolarization. BPA and TBBPA both interfere with skeletal muscle function through divergent mechanisms that impair excitation-contraction coupling and may be exemplary of their adverse outcomes in other muscle types.

Original languageEnglish (US)
Pages (from-to)428-436
Number of pages9
JournalMolecular Pharmacology
Volume91
Issue number4
DOIs
StatePublished - Apr 1 2017

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Muscles
Sarcoplasmic Reticulum
L-Type Calcium Channels
Ryanodine Receptor Calcium Release Channel
Calcium-Transporting ATPases
Skeletal Muscle Fibers
Microsomes
Endoplasmic Reticulum
Skeletal Muscle
Endocrine Disruptors
Excitation Contraction Coupling
Membrane Potentials
bisphenol A
tetrabromobisphenol A

ASJC Scopus subject areas

  • Medicine(all)
  • Molecular Medicine
  • Pharmacology

Cite this

Divergent Mechanisms Leading to Signaling Dysfunction in Embryonic Muscle by Bisphenol A and Tetrabromobisphenol A. / Zhang, Rui; Pessah, Isaac N.

In: Molecular Pharmacology, Vol. 91, No. 4, 01.04.2017, p. 428-436.

Research output: Contribution to journalArticle

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