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¹ Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA

Considerable work over the past two decades has determined that interstitial cells of Cajal (ICC) serve as pacemaker cells, conduits for active transmission of electrical slow waves, sites of innervation by peripheral motor neurons, and mechanotransducers. While most of the physiology of ICC has been learned from studies of the cells within the gastrointestinal tract, ICC are found in a variety of smooth muscle tissues and may have analogous or novel physiological functions in those organs. Clinical investigations of muscles from patients with a variety of gastrointestinal motility disorders have raised the exciting possibility that loss of ICC may be responsible for the development of motor dysfunction. This review discusses the development of ICC, the kinds of human disorders in which ICC loss may be important, what factors regulate the ICC phenotype, and what therapeutic approaches might be utilized to restore or regenerate ICC. This field is primed for translational discoveries. ICC are responsible for critical physiological functions in smooth muscle tissues, they are lost in pathophysiological conditions, and it will be important now to decipher the conditions that are responsible for ICC loss and develop new therapies to relieve patients of this problem. Success in this endeavour might improve the quality of life for millions of patients.

(Received 8 July 2006; accepted after revision 30 August 2006; first published online 31 August 2006)
Corresponding author K. M. Sanders: Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557 USA. Email: kent{at}unr.edu

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