Spontaneous Activity in Urethral Smooth Muscle.

The urethra is a muscular tube that extends from the bladder neck and is composed of an inner layer of smooth muscle referred to as the internal urethral sphincter and an outer layer of striated muscle which forms the external urethral sphincter. The smooth muscle layer can be separated into an inner layer of longitudinally orientated smooth muscle and an outer, relatively thinner, layer of circular muscle. Tonic contraction of both the smooth and striated muscle components of the urethra generates a urethral closure pressure which exceeds intravesical pressure in the bladder to maintain urinary continence. It is likely that contraction of urethral smooth muscle is involved in the long-term maintenance of tone, since it can achieve this at relatively low energy cost, whereas the striated muscle contributes more to the rise in urethral tone that accompanies increases in bladder pressure secondary to coughing or other sudden increases in intra-abdominal pressure. The level of urethral smooth muscle tone is regulated by several autonomic neurotransmitters, including noradrenaline, acetylcholine, ATP and nitric oxide. However, it is also clear that urethral smooth muscle is capable of generating significant tone in the absence of neural input. In this chapter we will discuss the mechanisms responsible for contraction of urethral smooth muscle, with specific focus on the role of ion channels and Ca handling proteins to this process. The mechanisms underlying spontaneous activity in urethral interstitial cells (UICs), putative pacemaker cells of the urethra, will also be examined along with the modulation of these mechanisms by key excitatory and inhibitory neurotransmitters.