Expression of Type 3 Acid Sensitive Ion Channels in Bladder of OAB Rat Model

LIU Xiao-dong, CHEN Jian-heng, LI Hai-yuan. et al

Abstract

To investigate the expression of type 3 acid-sensing ion channels (ASIC3) in bladder tissue of over active bladder (OAB) rat model. Methods Sixty adult female rats were randomly divided into control group (intraperitoneal injection of 0.9%sodium chloride), OAB group (intraperitoneal injection of cyclophosphamide) and the intervention group (OAB rats treated with ASIC3 inhibitor amiloride). The rats underwent urodynamic testing. The bladder tissues were collected for pathological examination, while the expressions of ASIC3 were measured by the methods of immunohistochemistry, RT-PCR and Western blot. Results Urodynamic study found that the rats in control group had no significant contraction instability in both storage and voiding stages. Compared with the control group, OAB group and intervention group showed instability of visible contraction in urine storage stage, with shorter micturition interval ( P<0.01) and increased frequency of urination ( P<0.01). Compared with the OAB group, the intervention group showed significantly prolonged micturition interval ( P<0.05) and reduced frequency of urination ( P<0.05). Pathologic examination showed rat bladder mucosal damage in both OAB group and intervention group. Immunohistochemistry found the expression of ASIC3 on bladder mucosa. RT-PCR and Western blot showed significantly higher expression of ASIC3 in OAB group ( P<0.01), but the expression of ASIC3 decreased in intervention group after adding ASIC3 inhibitor.Conclusion ASIC3 expresses mainly on bladder mucosa. The gene and protein expression of ASIC3 in rat bladder tissue of OAB rats is higher, which can be significantly decreased by ASIC inhibitor.The symptoms of OAB reduce after intervention, which demonstrates the increased expression of ASIC3 in bladder tissue is closely related to bladder detrusor.

 

Keywords: Type 3 of acid-sensing ion channels, Over active bladder, Amiloride 

 

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References


Abrams P. Cardozo I, Fall M. et al. The standardisation of terminology of lower urinary tract function; report from the standardisation sub-committee of the international continence society. Neurourol Urodyn,2002;21(2): 167-178.

Sanchez-Freire V, Blanchard MO, Burkhard FC, et al. Acid- sensing channels in human bladder: expression, function and alteration during bladder pain syndrome. J Urol,2011; 186(4); 1509-1516.

Tan ZY, Lu Y. Whiteis CA. et al. Chemoreceptor hypersensitivity, sympathetic excitation, and overexpression of ASIC and TASK channels before the onset of hypertension in SHR. Circ Res,2010; 106(3) ;536-545.

Rios ER, Rocha NF, Carvalho AM. et al. TRP and ASIC channels mediate the antinociceptive effect of citronellyl acetate. Chem Biol Interact,2013;203(3);573-579.

Gautam M, Benson CJ. Acid-sensing ion channels (ASICs) in mouse skeletal muscle afferents are heteromers composed of ASICla. ASIC2, and ASIC3 subunits. Chem Biol Interact, 2013;27(2);793-802.

Nitta CH. Osmond I)A. Herbert LM, et al. Role of ASIC1 in the development of chronic hypoxia-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol,2014 ; 306( 1): H41-H52.

Pan F, Liu d. Han XM. et al. Urodynamic investigation of cyclophosphamide-induced overactive bladder in conscious rats. Chin Med J (Engl) ,2012; 125(2) :321-325.

Ho DR, Chen CS, Lin WY, et al. Effect of hyaluronic acid on urine nerve growth factor in cyclophosphamide-induced cystitis. Int J Urol*2011; 18(7);525-531.

Anderson UA, Carson C, McCloskey KD. KCNQ currents and their contribution to resting membrane potential and the excitability of interstitial cells of Cajal from the guinea pig bladder. J Urol.2009; 182( 1):330-336.

He P, Deng J, Zhong X, et al. Identification of a hyerpolarization-activated cyclic nucleotide-gated channel and its subtypes is the urinary bladder of the rat. Urology, 2012; 79(6): 1411. e7-13. doi: 10. 1016/j. urology. 2012. 01. 037. Parsons CL. The role of a leaky epithelium and potassium in the generation of bladder symptoms in interstitial cystitis/ overactive bladder, urethral syndrome, prostatitis and gynaecological chronic pelvic pain. BJU Int,2011;107(3):370- 375.

Parsons CL. The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology,2007;69(4) :S9-S16.

Jing L, Chu XP. Jiang YQ, et al. N-glycosylation of acid- sensing ion channel la regulates its trafficking and acidosis- induced spine remodeling. J Neurosci, 2012; 32 ( 12 ); 4080- 4091.

Babinski K, Catarsi S, Biagini G, et al. Mammalian ASIC2a and ASIC3 subunits со-assemble into heteromeric proton-gated channels sensitive to Gd3 +. J Biol Client, 2000; 275 ( 37 ); 28519-28525.


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