title: 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.
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Dongyang
authors.initials: D
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Ce
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Hongchao
authors.initials: H
authors.lastname: Men
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China.
authors.forename: Xiaona
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China; School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK. Electronic address: N.Gamper@leeds.ac.uk.
authors.forename: Nikita
authors.initials: N
authors.lastname: Gamper
authors.affiliation: Department of Pharmacology, Hebei Medical University, Shijiazhuang, PR China. Electronic address: zhanghl@hebmu.edu.cn.
authors.forename: Hailin
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000255:Adenosine Triphosphate / Q000276:immunology; D000818:Animals; D001920:Bradykinin / Q000276:immunology*; D020747:Calcium Channels, T-Type / Q000032:analysis / Q000276:immunology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000276:immunology; D005727:Ganglia, Spinal / Q000166:cytology* / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D009638:Norepinephrine / Q000276:immunology; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000166:cytology / Q000276:immunology*
chemical_list: D020747:Calcium Channels, T-Type; D000255:Adenosine Triphosphate; D015232:Dinoprostone; D001920:Bradykinin; D009638:Norepinephrine
keywords: Bradykinin; Inflammation; Nociceptor; P2Y receptors; Prostaglandin; T-type Ca(2+) channels