Contractile protein changes in urinary bladder smooth muscle following outlet obstruction.

Abstract

Force production by the bladder body smooth muscle and relaxation of the bladder outlet, required for bladder emptying, are regulated by Ca2+ via myosin light chain (MLC) phosphorylation by a Ca2+-calmodulin-dependent MLC kinase (for review, 1–3). Besides this mode of regulation, evidence from most laboratories, including ours, supports the existence of a thin-filament-mediated regulation due to protein-protein interaction by actin-binding proteins acting in concert with tropomyosin and a calcium-binding protein, most likely, calmodulin. Caldesmon (CaD), a thin-filament-associated protein, inhibits the ac-tin-myosin interaction and actomyosin ATPase, and this inhibition is reversed by calmodulin in the presence of Ca2+.3–5 Urinary bladder outlet obstruction interferes with the ability of the bladder to empty its contents, thereby inducing changes in the bladder wall smooth muscle cells which enable the bladder to produce the increased contractile force required to expel urine through the obstructed urethra. In the initial phases of outlet obstruction, there is transient decompensation of the bladder smooth muscle, which initiates the molecular events that lead to hypertrophy of the detrusor smooth muscle cells enabling it to generate and maintain force. However, continuation of the outlet obstruction induces molecular, cellular, and structural alterations in the muscle cells of the bladder wall, leading ultimately to decreased compliance and impaired emptying. The ability of smooth muscles to compensate for increased functional demand is associated with alterations in the expression of proteins in the thick- and thin-filaments.