Interstitial cell of Cajal

The interstitial cell of Cajal (ICC) is a type of interstitial cell found in the gastrointestinal tract. There are different types with different functions. Myenteric Interstitial cells of Cajal (ICC-MY) serve as a pacemaker which creates the bioelectrical slow wave potential that leads to contraction of the smooth muscle. Intramuscular Interstitial cells of Cajal (ICC-IM) are involved in the stimulation of smooth muscle cells, neurotransmitters act through them. Certain calcium-activated chloride channels are now known to play an important role in regulating human gastrointestinal ICC, particularly the anoctamin channel ANO1. A recent review noted that carbachol increases ICC activity through this channel. ANO1-knockout mice fail to produce slow waves and ANO1 channel inhibitors in humans block slow wave production. Many types of smooth muscle tissues have now been shown to contain ICC, but with few exceptions the function of these cells is not known and is currently an area of active research. These cells are derived from mesoderm. ICC serve as electrical pacemakers and generate spontaneous electrical slow waves in the gastrointestinal (GI) tract. Electrical slow waves spread from ICC to smooth muscle cells and the resulting depolarization initiates calcium ion entry and contraction. Slow waves organize gut contractions into phasic contractions that are the basis for peristalsis and segmentation. The frequency of ICC pacemaker activity differs in different regions of the GI tract: ICC also mediate neural input from enteric motor neurons. Animals lacking ICC have greatly reduced responses to the neurotransmitter acetylcholine, released from excitatory motor neurons, and to the transmitter nitric oxide, released from inhibitory motor neurons. Loss of ICC in disease, therefore, may interrupt normal neural control of gastrointestinal (GI) contractions and lead to functional GI disorders, such as irritable bowel syndrome. ICC also express mechano-sensitive mechanisms that cause these cells to respond to stretch. Stretching GI muscles can affect the resting potentials of ICC and affect the frequency of pacemaker activity. Carbachol increases ICC activity through ANO1 activation.