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Chronic interleukin‐6 exposure alters metabotropic glutamate receptor‐activated calcium signalling in cerebellar Purkinje neurons
Author(s) -
Nelson Thomas E.,
Netzeband Jeffrey G.,
Gruol Donna L.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03706.x
Subject(s) - ryanodine receptor , metabotropic glutamate receptor , metabotropic receptor , glutamate receptor , cerebellum , biology , neuroscience , medicine , endocrinology , afterhyperpolarization , agonist , intracellular , receptor , chemistry , microbiology and biotechnology , electrophysiology
Chronic central nervous system expression of the cytokine interleukin‐6 (IL‐6) is thought to contribute to the histopathological, pathophysiological, and cognitive deficits associated with various neurological disorders. However, the effects of chronic IL‐6 expression on neuronal function are largely unknown. Previous studies have shown that chronic IL‐6 exposure alters intrinsic electrophysiological properties and intracellular Ca 2+ signalling evoked by ionotropic glutamate receptor activation in cerebellar Purkinje neurons. In the current study, using primary cultures of rat cerebellum, we investigated the effects of chronic IL‐6 exposure on metabotropic glutamate receptor (mGluR)‐activated Ca 2+ signalling and release from intracellular Ca 2+ stores. Chronic exposure (6–10 days) of Purkinje neurons to 500 units/mL IL‐6 resulted in elevated resting Ca 2+ levels and increased intracellular Ca 2+ signals evoked by the group I mGluR agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG) compared to untreated control neurons. Chronic IL‐6 treatment also augmented Ca 2+ signals evoked by brief 100 m m K + depolarization, although to a lesser degree than responses evoked by DHPG. Depleting intracellular Ca 2+ stores with sarcoplasmic‐endoplasmic reticulum ATPase inhibitors (thapsigargin or cyclopiazonic acid) or blocking ryanodine receptor‐dependent release from intracellular stores (using ryanodine) resulted in a greater reduction of DHPG‐ and K + ‐evoked Ca 2+ signals in chronic IL‐6‐treated neurons than in control neurons. The present data show that chronic exposure to elevated levels of IL‐6, such as occurs in various neurological diseases, alters Ca 2+ signalling involving release from intracellular stores. The results support the hypothesis that chronic IL‐6 exposure disrupts neuronal function and thereby may contribute to the pathophysiology associated with many neurological diseases.