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Inflammatory mediator bradykinin increases population of sensory neurons expressing functional T-type Ca(2+) channels.

Abstract：

:T-type Ca(2+) channels are important regulators of peripheral sensory neuron excitability. Accordingly, T-type Ca(2+) currents are often increased in various pathological pain conditions, such as inflammation or nerve injury. Here we investigated effects of inflammation on functional expression of T-type Ca(2+) channels in small-diameter cultured dorsal root ganglion (DRG) neurons. We found that overnight treatment of DRG cultures with a cocktail of inflammatory mediators bradykinin (BK), adenosine triphosphate (ATP), norepinephrine (NE) and prostaglandin E2 (PGE2) strongly increased the population size of the small-diameter neurons displaying low-voltage activated (LVA, T-type) Ca(2+) currents while having no effect on the peak LVA current amplitude. When applied individually, BK and ATP also increased the population size of LVA-positive neurons while NE and PGE2 had no effect. The PLC inhibitor U-73122 and B2 receptor antagonist, Hoe-140, both abolished the increase of the population of LVA-positive DRG neurons. Inflammatory treatment did not affect CaV3.2 mRNA or protein levels in DRG cultures. Furthermore, an ubiquitination inhibitor, MG132, did not increase the population of LVA-positive neurons. Our data suggest that inflammatory mediators BK and ATP increase the abundance of LVA-positive DRG neurons in total neuronal population by stimulating the recruitment of a 'reserve pool' of CaV3.2 channels, particularly in neurons that do not display measurable LVA currents under control conditions.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Huang D,Liang C,Zhang F,Men H,Du X,Gamper N,Zhang H

doi

10.1016/j.bbrc.2016.02.118

subject

Has Abstract

pub_date

2016-04-29 00:00:00

pages

396-402

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(16)30306-0

journal_volume

473

pub_type

杂志文章

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