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Expressions of voltage-gated K+ channel 2.1 and 2.2 in rat bladder with detrusor hyperreflexia
Authors:Gan Xiu-guo  An Rui-hua  Bai Yu-feng  Zong De-bin
Affiliation:Department of Urology, First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China
Abstract:Background Voltage-gated K+channel(KV)plays a critical role in the modulation of detrusor contraction.This study was conducted to investigate the expressions of Kv2.1 and Kv2.2 in rat bladder with detrusor hyperreflexia(DH).Methods Thirty adult female Sprague-Dawley rats(200-220 g)were randomly divided into the control group and the experimental group.The experimental group was subjected to spinal cord injury(SCI).In the controls,the surgical procedure was identical with the exception that dura and spinal cord were transected.Four weeks after SCI,in vivo cystometry and mechanical pulling tests of isolated detrusor strips were performed.mRNA was extracted from the detrusors of normal and DH rats for the detection of expression of Kv2.1 and Kv2.2 by RT.PCR.Differences in expression between normal and overactive detrusors were identified by gel imaging.Results Fourteen rats in the experimental group exhibited uninhibited bladder contraction(>8 cmH20)before voiding after SCl.One rat died from infection.The frequency of DH in the experimental group was significantly different from that in the control group with or without treatment with 4-aminopyridine(4-AP)(P<0.05),while the amplitude of DH did not change markedly.The rates of variation of the automatic contractile frequency and amplitude were(66.8-+1 2.4)%and (42.6±12.6)%respectively in the control group,and(38.4±9.8)%and(28.0±4.6)% respectively in the DH group.4-AP increased the automatic contractile frequency aDart from the automatic contractile amplitude in both the control and DH groups(P<0.05).4-AP increased the rate of variation of the automatic contractile frequency more markedly in the control group than in the DH group(P<0.05).Significant expression of Kv2.2 was not detected in bladders in the control group.Compared to the mRNA levels of 13-actin,the mRNA level of Kv2.1 was 1.26±0.12 in the control group and 0.66±0.08 in the DH group.SCI significantly reduced the mRNA level of Kv2.1 in rat bladders with DH (P<0.05).Conclusions Our study showed that the mRNA level of Kv2.1 decreased significantly in rat bladder with DH,which was one of the important pathogenetic mechanisms for DH,and suggested that Kv2.1 might be one of the therapeutic targets for bladder overactivity.
Keywords:potassium voltage-gated channel   overactive detrusor   spinal cord injury
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