INTRODUCTION One of the main functions of gastrointestinal smooth muscle is to provide an orderly pas- sage of food from the esophagus to the colon. This is achieved by the coordinated move- ments of the two main muscle layers, the lon- gitudinal and the circular muscle, under the influence of neuronal, hormonal, and myo- genic factors. Each of these factors affects the excitability of the smooth muscle cells that, in turn, are dependent on membrane ion chan- nels. The combination of molecular cloning with electrophysiology has helped define the individual ion channel components that gen- erate ionic currents in a variety of tissues, including gastrointestinal smooth muscle. These types of studies have not only improved our understanding of the molecular mecha- nisms in normal physiology but also of several pathophysiological states that result from defects in channel function denoted as “chan- nelopathies.” Genetic “channelopathies” have been recognized as defects in channel function Inflammation-Induced “Channelopathies” in the Gastrointestinal Smooth Muscle Anna P. Malykhina and Hamid I. Akbarali* Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, OK 73104 Abstract Inflammation markedly alters the motility patterns of the gastrointestinal tract, resulting mostly in decreased excitability of smooth muscle. There is emerging evidence indicating that inflamma- tion alters ion channel expression and function of smooth muscle cells. In this review we summa- rize studies defining the mechanisms affecting contractile and electrical activity of gastrointestinal smooth muscle. We have focused on the evidence for decreased calcium channel conductance and alterations in the intracellular signaling mechanisms and discuss the role of muscarinic receptor activation in models of gastrointestinal inflammation. We propose that some of the clinical symp- toms of altered smooth muscle contraction in pathogenesis of gut disorders such as inflammatory bowel disease may be regulated at the level of the ion channel. Index Entries: Gastrointestinal smooth muscle; contraction; ion channels; Src kinase; muscarinic receptors. *Author to whom all correspondence and reprint requests should be addressed. E-mail: hamid-akbarali@ ouhsc.edu. REVIEW ARTICLE © Copyright 2004 by Humana Press Inc. All rights of any nature whatsoever reserved. 1085-9195/04/41:319–330/$25.00 Cell Biochemistry and Biophysics 319 Volume 41, 2004