Ion channels in interstitial cells of Cajal as targets for neurotransmitter action

Interstitial cells of Cajal (ICC) are involved in generation of gut pacemaker activity, neurotransmission and stretch sensation. Pacemaker ICC exhibit spontaneous cyclic calcium oscillations that are in synchrony with its pacemaker activity. The spontaneous rhythmic inward currents in ICC that underlie gut pacemaker activity are linked to this calcium oscillation. It is probable that more than one type of channel contributes to the inward current with a high conductance chloride channel and a nonselective cation channel being the main candidates. The activation of these channels is linked to intracellular calcium cycling mechanism and involves inositol 1,4,5-trisphosphate (IP₃)-mediated calcium release from the sarcoplasmic reticulum, and calcium uptake into mitochondria. This ion channel activity is modulated by signalling through neurotransmitter receptors, including the NK₁ receptor. This finding and the presence of other neurotransmitter receptor mRNA transcripts indicates that ion channels in ICC are targets for neurotransmitter action. The ether-a-go-go-related (ERG) K channel is probably the most important K channel contributing to the resting membrane potential and excitability of the ICC. Many ion channels in ICC are regulated by second messenger systems which makes them highly susceptible to neurotransmitter modulation.