Presentation Title

Urinary bladder dysfunction in transient receptor potential vanilloid family member 4 (TRPV4) null and wildtype (WT) mice following spinal cord injury (SCI)

Abstract

Upper motor neuron SCI results in the inability to empty the bladder voluntarily, neurogenic detrusor overactivity (NDO), and detrusor sphincter dyssynergia (DSD). NDO and DSD cause incontinence, high-pressure or absent voiding, and large post-void residual volumes, renal damage, incontinence, and recurrent urinary tract infections. Current approaches to treat bladder dysfunction in SCI individuals are inadequate; novel approaches are required to restore continence with increased bladder capacity. TRP channel families are a superfamily of non-specific cation channels that may act as sensors of stretch and/or chemical irritation in the lower urinary tract. TRPV4 expression is present in urothelial cells and in the detrusor muscle but urothelial TRPV4 expression is ~20-36-fold greater. Contributions of TRPV4 to normal bladder function and bladder dysfunction, luminal ATP release and pelvic sensitivity have been demonstrated. In TRPV4 null and WT (C57Bl/6) mice, we continue to evaluate urinary bladder function in spinal intact state and following SCI using conscious cystometry and natural voiding assays (UroVoid) to determine functional bladder capacity and voiding efficiency. We report that SCI in TRPV4 null mice resulted in significant improvement in bladder function after SCI compared to WT mice. In TRPV4 null mice with SCI, the usual hyperreflexia was attenuated with normal bladder pressure, increased bladder capacity and voiding efficiency and automatic micturition was acquired earlier than in WT mice with SCI. Changes in the urinary bladder of TRPV4 null mice with SCI were also observed; detrusor hypertrophy that accompanies SCI was reduced. Mechanisms underlying the improvement in bladder function after SCI in TRPV4 null mice may suggest that the TRPV4/Ca2+ complex (1) contributes to the inflammatory environment of the spinal cord and/or (2) normally acts a brake involving BKCa and/or SKCa channels to elicit hyperpolarization.

Primary Faculty Mentor Name

Margaret Vizzard

Faculty/Staff Collaborators

Margaret A. Vizzard (Collaborating Mentor), Susan Campbell

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Health Sciences

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Urinary bladder dysfunction in transient receptor potential vanilloid family member 4 (TRPV4) null and wildtype (WT) mice following spinal cord injury (SCI)

Upper motor neuron SCI results in the inability to empty the bladder voluntarily, neurogenic detrusor overactivity (NDO), and detrusor sphincter dyssynergia (DSD). NDO and DSD cause incontinence, high-pressure or absent voiding, and large post-void residual volumes, renal damage, incontinence, and recurrent urinary tract infections. Current approaches to treat bladder dysfunction in SCI individuals are inadequate; novel approaches are required to restore continence with increased bladder capacity. TRP channel families are a superfamily of non-specific cation channels that may act as sensors of stretch and/or chemical irritation in the lower urinary tract. TRPV4 expression is present in urothelial cells and in the detrusor muscle but urothelial TRPV4 expression is ~20-36-fold greater. Contributions of TRPV4 to normal bladder function and bladder dysfunction, luminal ATP release and pelvic sensitivity have been demonstrated. In TRPV4 null and WT (C57Bl/6) mice, we continue to evaluate urinary bladder function in spinal intact state and following SCI using conscious cystometry and natural voiding assays (UroVoid) to determine functional bladder capacity and voiding efficiency. We report that SCI in TRPV4 null mice resulted in significant improvement in bladder function after SCI compared to WT mice. In TRPV4 null mice with SCI, the usual hyperreflexia was attenuated with normal bladder pressure, increased bladder capacity and voiding efficiency and automatic micturition was acquired earlier than in WT mice with SCI. Changes in the urinary bladder of TRPV4 null mice with SCI were also observed; detrusor hypertrophy that accompanies SCI was reduced. Mechanisms underlying the improvement in bladder function after SCI in TRPV4 null mice may suggest that the TRPV4/Ca2+ complex (1) contributes to the inflammatory environment of the spinal cord and/or (2) normally acts a brake involving BKCa and/or SKCa channels to elicit hyperpolarization.