Minding the calcium store: Ryanodine receptor activation as a convergent mechanism of PCB toxicity

Isaac N Pessah, Gennady Cherednichenko, Pamela J Lein

Research output: Contribution to journalArticle

147 Scopus citations

Abstract

Chronic low-level polychlorinated biphenyl (PCB) exposures remain a significant public health concern since results from epidemiological studies indicate that PCB burden is associated with immune system dysfunction, cardiovascular disease, and impairment of the developing nervous system. Of these various adverse health effects, developmental neurotoxicity has emerged as a particularly vulnerable endpoint in PCB toxicity. Arguably the most pervasive biological effects of PCBs could be mediated by their ability to alter the spatial and temporal fidelity of Ca2+ signals through one or more receptor-mediated processes. This review will focus on our current knowledge of the structure and function of ryanodine receptors (RyRs) in muscle and nerve cells and how PCBs and related non-coplanar structures alter these functions. The molecular and cellular mechanisms by which non-coplanar PCBs and related structures alter local and global Ca2+ signaling properties and the possible short and long-term consequences of these perturbations on neurodevelopment and neurodegeneration are reviewed.

Original languageEnglish (US)
Pages (from-to)260-285
Number of pages26
JournalPharmacology and Therapeutics
Volume125
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • Activity dependent plasticity
  • Bastadins
  • Calcium regulation
  • Calcium-induced calcium release
  • Developmental neurotoxicity
  • Polybrominated diphenylethers
  • Polychlorinated biphenyls
  • Ryanodine receptor (RyR)
  • Triclosan

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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