Spontaneous Electrical Activity and Rhythmicity in Gastrointestinal Smooth Muscles

The gastrointestinal (GI) tract has multifold tasks of ingesting, processing, and assimilating nutrients and disposing of wastes at appropriate times. These tasks are facilitated by several stereotypical motor patterns that build upon the intrinsic rhythmicity of the smooth muscles that generate phasic contractions in many regions of the gut. Phasic contractions result from a cyclical depolarization/repolarization cycle, known as electrical slow waves, which result from intrinsic pacemaker activity. Interstitial cells of Cajal (ICC) are electrically coupled to smooth muscle cells (SMCs) and generate and propagate pacemaker activity and slow waves. The mechanism of slow waves is dependent upon specialized conductances expressed by pacemaker ICC. The primary conductances responsible for slow waves in mice are Ano1, Ca²⁺-activated Cl^- channels (CaCCs), and Ca_V3.2, T-type, voltage-dependent Ca²⁺ channels. Release of Ca²⁺ from intracellular stores in ICC appears to be the initiator of pacemaker depolarizations, activation of T-type current provides voltage-dependent Ca²⁺ entry into ICC, as slow waves propagate through ICC networks, and Ca²⁺-induced Ca²⁺ release and activation of Ano1 in ICC amplifies slow wave depolarizations. Slow waves conduct to coupled SMCs, and depolarization elicited by these events enhances the open-probability of L-type voltage-dependent Ca²⁺ channels, promotes Ca²⁺ entry, and initiates contraction. Phasic contractions timed by the occurrence of slow waves provide the basis for motility patterns such as gastric peristalsis and segmentation. This chapter discusses the properties of ICC and proposed mechanism of electrical rhythmicity in GI muscles.