Over the past 20 years, many studies have given evidence that Interstitial cells of Cajal (ICC): (i) serve as pacemaker cells with unique ionic currents that generate electrical slow waves in GI muscles; (ii) provide a pathway for active slow wave propagation in GI organs; (iii) express receptors, transduction mechanisms and ionic conductances allowing them to mediate post-junctional responses to enteric motor neurotransmission; (iv) regulate smooth muscle excitability by contributing to resting potential and affecting syncytial conductance; and (v) manifest stretch-receptor functions regulating excitability and regulating slow wave frequency.