Ryanodine receptors contribute to the induction of ischemic tolerance

Brain Res Bull. 2016 Apr:122:45-53. doi: 10.1016/j.brainresbull.2016.02.018. Epub 2016 Feb 27.

Abstract

Ischemic tolerance (IT) is induced by a variety of insults to the brain (e.g., nonfatal ischemia, heat and hypoxia) and it provides a strong neuroprotective effect. Although the mechanisms are still not fully elucidated, Ca(2+) is regarded as a key mediator of IT. Ryanodine receptors (RyRs) are located in the sarcoplasmic/endoplasmic reticulum membrane and are responsible for the release of Ca(2+) from intracellular stores. In brain, neuronal RyRs are thought to play a role in various neuropathological conditions, including ischemia. The purpose of the present study was to investigate the involvement of RyRs in IT. Pretreatment with a RyR antagonist, dantrolene (25mg/kg, i.p), blocked IT in a gerbil global ischemia model, while a RyR agonist, caffeine (100mg/kg, i.p), stimulated the production of IT. In vitro, using rat hippocampal cells, short-term oxygen/glucose deprivation induced preconditioning and RyR antagonists, dantrolene (50 and 100 μM) and ryanodine (100 and 200 μM) prevented it. RyR protein and mRNA levels were transiently decreased after induction of IT. These results suggest that RyRs are involved in the induction of ischemic tolerance.

Keywords: CA1 hippocampal cells; Cell culture; Intracellular Ca(2+); Ischemic tolerance; Oxygen glucose deprivation; Ryanodine receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / metabolism*
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / metabolism
  • Caffeine / pharmacology
  • Calcium / metabolism
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Signaling
  • Cells, Cultured
  • Endoplasmic Reticulum / drug effects
  • Endoplasmic Reticulum / metabolism
  • Gerbillinae
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Male
  • Neurons / drug effects
  • Rats
  • Ryanodine Receptor Calcium Release Channel / metabolism*
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism

Substances

  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Inositol 1,4,5-Trisphosphate Receptors
  • Ryanodine Receptor Calcium Release Channel
  • Caffeine
  • Calcium