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Enhanced Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channel in Primary Sensory Neurons in Diabetic Rats
Song Zhenyuan 1 #,Hu Ji 1,Zhang Honghong 1,Xu Guangyin 2 *
1.Division of Endocrinology, the Second Affiliated Hospital, Soochow University, Suzhou 215000, P.R. China
2.Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases
*Correspondence author
#Submitted by
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Funding: none
Opened online:25 May 2015
Accepted by: none
Citation: Song Zhenyuan,Hu Ji,Zhang Honghong.Enhanced Colonic Hypersensitivity and Sensitization of Voltage-gated Sodium Channel in Primary Sensory Neurons in Diabetic Rats[OL]. [25 May 2015] http://en.paper.edu.cn/en_releasepaper/content/4644279
 
 
Background: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. This study was designed to determine roles of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) in colonic hypersensitivity of diabetic rats. Methods: Diabetic models were induced by a single intraperitoneal injection of Streptozotocin (STZ; 65 mg/kg i.p.) in adult female rats. Behavioral responses to colorectal distention (CRD) were used to determine colonic sensitivity in rats. Colon-specific DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. Results: STZ injection produced a significantly lower distention threshold than control rats in responding to CRD. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased number of action potentials evoked by 2 and 3 times rheobase stimulation and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. Conclusion: Our results suggest that enhanced neuronal excitability following STZ injection, which might be mediated by upregulation of NaV1.7 and NaV1.8 expression in primary sensory neurons, may play an important role in diabetic colonic hypersensitivity.
Keywords:Diabetes; Colonic hypersensitivity; Dorsal root ganglion; Voltage-gated sodium channels
 
 
 

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