Ionic conductances regulating the excitability of colonic smooth muscles

Abstract

The tunica muscularis of the gastrointestinal (GI) tract contains two layers of smooth muscle cells (SMC) oriented perpendicular to each other. SMC express a variety of voltage-dependent and voltage-independent ionic conductance(s) that develop membrane potential and control excitability. Resting membrane potentials (RMP) vary through the GI tract but generally are within the range of -80 to -40 mV. RMP sets the 'gain' of smooth muscle and regulates openings of voltage-dependent Ca(2+) channels. A variety of K(+) channels contribute to setting RMP of SMC. In most regions, RMP is considerably less negative than the K(+) equilibrium potential, due to a finely tuned balance between background K(+) channels and non-selective cation channels (NSCC). Variations in expression patterns and openings of K(+) channels and NSCC account for differences of the RMP in different regions of the GI tract. Smooth muscle excitability is also regulated by interstitial cells (interstitial cells of Cajal (ICC) and PDGFRα(+) cells) that express additional conductances and are electrically coupled to SMC. Thus, 'myogenic' activity results from the integrated behavior of the SMC/ICC/PDGFRα(+) cell (SIP) syncytium. Inputs from excitatory and inhibitory motor neurons are required to produce the complex motor patterns of the gut. Motor neurons innervate three cell types in the SIP, and receptors, second messenger pathways, and ion channels in these cells mediate postjunctional responses. Studies of isolated SIP cells have begun to unravel the mechanisms responsible for neural responses. This review discusses ion channels that set and regulate RMP of SIP cells and how neurotransmitters regulate membrane potential.