Abnormal calcium homeostasis in peripheral neuropathies

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Cell Calcium. 2009 Dec 22

Abnormal calcium homeostasis in peripheral neuropathies.

Fernyhough P, Calcutt NA.

Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg,

Manitoba, Canada R3E 0T6; Division of Neurodegenerative Disorders, St Boniface

Hospital Research Centre, Winnipeg, Manitoba, Canada R2H 2A6.

Abnormal neuronal calcium (Ca(2+)) homeostasis has been implicated in numerous

diseases of the nervous system. The pathogenesis of two increasingly common

disorders of the peripheral nervous system, namely neuropathic pain and diabetic

polyneuropathy, has been associated with aberrant Ca(2+) channel expression and

function.

Here we review the current state of knowledge regarding the role of Ca(2+)

dyshomeostasis and associated mitochondrial dysfunction in painful and diabetic

neuropathies. The central impact of both alterations of Ca(2+) signalling at the

plasma membrane and also intracellular Ca(2+) handling on sensory neurone

function is discussed and related to abnormal endoplasmic reticulum performance.

We also present new data highlighting sub-optimal axonal Ca(2+) signalling in

diabetic neuropathy and discuss the putative role for this abnormality in the

induction of axonal degeneration in peripheral neuropathies. The accumulating

evidence implicating Ca(2+) dysregulation in both painful and degenerative

neuropathies, along with recent advances in understanding of regional variations

in Ca(2+) channel and pump structures, makes modulation of neuronal Ca(2+)

handling an increasingly viable approach for therapeutic interventions against

the painful and degenerative aspects of many peripheral neuropathies.