SUFU 2018: Myogenic Mechanisms of Detrusor Overactivity in Spinal Cord Injury

Austin, TX (UroToday.com) The bladder has the unique capability of maintaining low muscle excitability during filling. Dr. Haeyeong Lee and colleagues discovered and characterized an entirely novel control mechanism that regulates detrusor excitability. PDGFRα+ cells supply a powerful inhibitory mechanism to the bladder during filling. This mechanism is composed of the following molecular and functional components: 1) PDGFRα+ cells display strong expression of SK3 channels (Kcnn3). 2) Hyperpolarization due to activation of SK channels in PDGFRα+ cells exerts a membrane potential-stabilizing effect on detrusor muscles. 3) Expression of TRPV4 channels provides a stretch-dependent source for Ca2+ entry and activation of SK channels. 4) Genetic deactivation of TRPV4 and SK3 channels result in bladder overactivity. The author’s hypothesis is the loss or defects in PDGFRα+ cells or in key molecular components of the inhibitory regulation provided by PDGFRα+ cells in spinal cord injury (SCI) leads to detrusor dysfunction and development of an overactive phenotype.

The authors had SCI which had induced by complete compression of T13-L1 spinal cord. Experiments were performed on 24 hr, 48 hr and 72 hr after surgery, then employed molecular approaches (RNAseq, qPCR and protein studies) and ex vivo cystometry.

They got in ex vivo cystometry, SCI bladder revealed an increase in the amplitude and frequency of transient contractions (TCs; relevant to non-voiding contractions in in-vivo cystometry) during filling. TCs increased in SCI bladders. Effects of a SK blocker (apamin) and a SK channel activator (SKA31) on TCs were reduced in SCI mice compared to control suggesting down-regulation of SK channels in SCI bladder. qPCR, immunohistochemistry and immunoblot showed the loss of PDGFRa and down-regulation of SK channels. RNAseq and qPCR data showed the apoptosis-related geneset score was significantly increased in SCI detrusor muscles.

Their findings support that loss or down-regulation of PDGFRα+ cells and SK channels in SCI detrusors might involve the development of detrusor overactivity from SCI.

Presented by: Haeyeong Lee, PhD

Authors: Haeyeong Lee PhD, Byoung Koh BS, Robert Corrigan BS, Andrew Yanez , Tong Zhou PhD, Kenton Sanders PhD and Sang Koh MD,PhD, University of Nevada, Reno, School of Medicine, Department of Physiology and Cell Biology

Written by: Bilal Farhan, MD, Female Urology Fellow and Voiding Dysfunction, Department of Urology, University of California, Irvine at the Society of Urodynamics, Female Pelvic Medicine & Urogenital Reconstruction Winter Meeting (SUFU 2018), February 27-March 3, 2018, Austin, Texas

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