Intramuscular interstitial cells of Cajal (ICC-IM) are involved in mediating responses to neurotransmission. All ICC in the gastrointestinal tract express calcium-activated chloride channels encoded by the gene
ANO1. These channels are activated by release of calcium in ICC and are important for both the pacemaker activity of ICC and their responses to neurotransmitters. A recent review noted that
carbachol increases ICC activity through this channel. ANO1-knockout mice fail to produce slow waves and ANO1 channel inhibitors block slow waves. 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.
Frequency of ICC pacemaker cells The frequency of ICC pacemaker activity differs in different regions of the GI tract: • 3 per minute in the
stomach • 12 per minute in the
duodenum • 9 per minute in the
ileum • 3 per minute in the
colon 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. ICC are also critical in the propagation of electrical slow waves. ICC form a network through which slow wave activity can propagate. If this network is broken, then 2 regions of muscle will function independently. ==Pathology==