Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid

Molecular Pain

Yaozong Yuan²  Weiyan Yao²  Dong Tang²  Xinqiu Liu¹  Yong Li³  Dandan Song²  Aihua Qian² 

[1] Department of Neurobiology, Shanghai Jiaotong University School of Medicine, Shanghai, China;Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China;Department of Biochemistry and Molecular Cell Biology, Shanghai Jiaotong University School of Medicine, Shanghai, China

关键词: [Ca²⁺]_i;    Voltage gated calcium channels;    Visceral sensory;    TNBS;    Dorsal root ganglia;   

Others  :  862546
DOI  :  10.1186/1744-8069-9-15

 received in 2012-09-16, accepted in 2013-03-22,  发布年份 2013

【 摘 要 】

Background

Visceral pain is common symptom involved in many gastrointestinal disorders such as inflammatory bowel disease. The underlying molecular mechanisms remain elusive. We investigated the molecular mechanisms and the role for voltage gated calcium channel (VGCC) in the pathogenesis in a rat model of 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced visceral inflammatory hypersensitivity.

Results

Using Agilent cDNA arrays, we found 172 genes changed significantly in dorsal root ganglia (DRG) of TNBS treated rats. Among these changed genes, Cav1.2 and Cav2.3 were significantly up-regulated. Then the RT-PCR and Western blot further confirmed the up-regulation of Cav1.2 and Cav2.3. The whole cell patch clamp recording of acutely dissociated colonic specific DRG neurons showed that the peak I_Ba density was significantly increased in colonic neurons of TNBS treated rats compared with control rats (−127.82 ± 20.82 pA/pF Vs −91.67 ± 19.02 pA/pF, n = 9, *P < 0.05). To distinguish the different type of calcium currents with the corresponding selective channel blockers, we found that L-type (−38.56 ± 3.97 pA/pF Vs −25.75 ± 3.35 pA/pF, n = 9, * P < 0.05) and R-type (−13.31 ± 1.36 pA/pF Vs −8.60 ± 1.25 pA/pF, n = 9, * P < 0.05) calcium current density were significantly increased in colonic DRG neurons of TNBS treated rats compared with control rats. In addition, pharmacological blockade with L-type antagonist (nimodipine) and R-type antagonist (SNX-482) with intrathecal injection attenuates visceral pain in TNBS induced inflammatory visceral hypersensitivity.

Conclusion

Cav1.2 and Cav2.3 in colonic primary sensory neurons play an important role in visceral inflammatory hyperalgesia, which maybe the potential therapeutic targets.

【 授权许可】

   
2013 Qian et al.; licensee BioMed Central Ltd.

【 图 表 】

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