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Spinal Cord Injury Upregulates TRPM4 in the Urinary Bladder
Author(s) -
Kullmann F Aura,
Beckel Jonathan,
Nakagomi Hiroshi,
WolfJohnston Amanda,
Gauthier Christian,
Kanai Anthony,
Birder Lori
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.666.15
Subject(s) - urothelium , detrusor muscle , spinal cord injury , muscle hypertrophy , urinary bladder , hyperplasia , cystometry , urothelial cell , medicine , endocrinology , downregulation and upregulation , myocyte , urology , spinal cord , chemistry , biochemistry , psychiatry , gene
Spinal cord injury (SCI) profoundly alters bladder function. Chronically, it induces urothelial hyperplasia, smooth muscle hypertrophy and detrusor hyperactivity, all of which prevent the bladder from properly storing and releasing urine. Transient receptor potential melastatin 4 (TRPM4) is a non‐selective cation channel activated by intracellular Ca 2+ and modulated by ATP. This channel has been implicated in various pathologies including SCI, inflammation, axonal degeneration and cardiac myocyte hypertrophy. We hypothesize that TRPM4 may play a role in bladder dysfunction after SCI. Here, we evaluated the expression and function of TRPM4 in the bladder urothelium and smooth muscle after SCI. Bladders were removed from control and spinal cord transected C57Bl6 female mice (T8‐T9; 1‐42 days post SCI). The mucosa and smooth muscle were separated surgically and used for RT‐PCR, western blot analysis, urothelial cell culture and muscle strips contractility studies. TRPM4 mRNA and protein were expressed in the mucosa and detrusor and were upregulated after SCI. Expression levels peaked at 3‐7 days post SCI and remained elevated for the duration of the study (6 weeks post SCI). Peak levels coincided with urothelial hyperplasia and smooth muscle hypertrophy following SCI. The TRPM4 antagonist, 9‐Phenanthrol (0.1‐30 µM), relaxed detrusor strips pre‐contracted with prostaglandin‐E2 (1µM) or carbachol (0.1µM) and reduced spontaneous activity. After SCI, the magnitude of these effects was increased. Our data reveal that TRPM4 is expressed in the bladder mucosa and detrusor and is upregulated after SCI, supporting the hypothesis that TRPM4 is involved in the remodeling processes and/or development of detrusor overactivity following SCI.