The Physiology and Pathophysiology of Interstitial Cells of Cajal: Pacemaking, Innervation, and Stretch Sensation

Interstitial cells of Cajal (ICC) are part of the control system that orchestrates and regulates a diverse set of motor patterns in all parts of the gut to facilitate absorption, transit, neural innervation, stretch sensation, and bacterial homeostasis. ICC are unique cells that either have intrinsic pacemaker activity, or can perform stimulus-induced pacemaking; they act as networks and this network is connected to inhibitory and excitatory intrinsic and extrinsic nerves that influence the ICC network. Ultimately, it is the smooth muscle cells that generate contractile activity. The smooth muscle cells respond to stimuli to contract; all stimuli affect the electrical activity of the smooth muscle cells that regulates calcium influx, the trigger for contraction. The primary stimulus is depolarization, which is received from ICC in a rhythmic fashion and from other stimuli such as distention or neurotransmitters interacting with the numerous receptors on its surface. Many patterns of contractions are determined by the rhythmic depolarization coming from a single ICC network, or are determined by more complex changes in electrical activity as a consequence of interaction of pacemaker activities coming from different ICC networks. The amplitude of contractions is determined by the absolute membrane potential, how far it reaches above threshold for calcium channel activation.