Recent advances in detrusor muscle function

Abstract

Contractile activation of detrusor smooth muscle is initiated by the release of transmitters from motor nerves. Acetylcholine is a ubiquitous transmitter, as also is adenosine triphosphate (ATP) in many animal bladders and in people from several patient groups with pathological bladder function. In recent years there has been progress in explaining several cellular mechanisms that link transmitter release to contraction and these will be considered. The lifetime of ATP in the neuromuscular junction is finite and broken down ultimately to adenosine, which can exert modulatory control of contractile activation. Adenosine depresses nerve-mediated contractions and two sites of action have been proposed: an action on the motor nerves via A[Formula: See Text] receptors to depress further transmitter release and a less well-defined depressant effect on the detrusor muscle. The Ca[Formula: See Text] ions that activate the contractile proteins are derived from intracellular stores, which releases their content via IP[Formula: See Text] receptor activation and Ca[Formula: See Text]-induced Ca[Formula: See Text] release. Filling of the stores in the rest interval is mediated via transmembrane flux of Ca[Formula: See Text] through Ca[Formula: See Text] channels. Activation of the channels is regulated by the level of the intracellular [Ca[Formula: See Text]], via activation and inactivation of Ca[Formula: See Text]-sensitive K[Formula: See Text] channels. Thus, Ca store filling is regulated by intracellular [Ca[Formula: See Text]] via a negative feedback process. The presence and physiological function of spontaneous contractions in detrusor remain contentious and little is known about their origin. One possibility is that they originate from random Ca[Formula: See Text] sparks, i.e. localized transient increases of [Ca[Formula: See Text]] that may eventually progress to generate a cellular Ca[Formula: See Text] transient. Observations by confocal microscopy have revealed the presence of such sparks, especially near the cell membrane, and thus provide a cellular basis for spontaneous contractions. Finally, the questions arises as to whether detrusor smooth muscle is a functional syncitium. The demonstration of small gap junctions by electron microscopy and the demonstration of the gap junction protein connexin45 indicate that the muscle mass may indeed be functionally connected. The implications regarding the spread of excitation are discussed.

• Adenosine Receptors
• Detrusor Smooth Muscle
• Gap Junctions
• Intracellular Calcium Stores
• Spontaneous Contractions