Role of Sarco/Endoplasmic Reticulum Calcium ATPase in Lower Urinary Tract Smooth Muscles

The control of intracellular Ca (2+) is central to the regulation of smooth muscle contractility. A defect in sarco/endoplasmic reticulum calcium ATPase (SERCA) activity and its expression level has been suggested as a major pathology in cardiac dysfunction. Recent studies have demonstrated that the increased expression of SERCA2a improves myocardial contractility and Ca (2+) handling in disease conditions. The therapeutic transfer of SERCA has been tried in an animal heart failure model with promising results. We know that SERCA also plays a major role in regulation of Ca (2+) in detrusor contraction and may affect the functional outcome after outlet obstruction and ischemia/reperfusion injury. Therefore, this may be a new target to improve muscle function in the lower urinary tract. We have performed studies using the application SERCA gene transfer into the rat urethra, demonstrating favorable results for the protection of urethral sphincteric muscle function from vaginal distension-induced injury. The therapeutic transfer of SERCA may be a novel approach for gene therapy to treat lower urinary tract pathology, including underactive bladder and stress urinary incontinence.