Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum |
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Authors: | Lee Hyun-Tai Hennig Grant W Fleming Neal W Keef Kathleen D Spencer Nick J Ward Sean M Sanders Kenton M Smith Terence K |
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Institution: | Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA. |
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Abstract: | BACKGROUND & AIMS: Like the heart, intestinal smooth muscles exhibit electrical rhythmicity, which originates in pacemaker cells surrounding the myenteric plexus, called interstitial cells of Cajal (ICC-MY). In large mammals, ICC also line septa (ICC-SEP) between circular muscle (CM) bundles, suggesting they might be necessary for activating muscle bundles. It is important to determine their functional significance, because a loss of ICC in humans is associated with disordered motility. Our aims were therefore to determine the role of ICC-SEP in activating the thick CM in the human jejunum. METHODS: The mucosa and submucosa were removed and muscle strips were cut and pinned in cross-section so that the ICC-MY and ICC-SEP networks and the CM could be readily visualized. The ICC networks and CM were loaded with the Ca(2+) indicator fluo-4, and pacemaker and muscle activity was recorded at 36.5 +/- 0.5( degrees )C. RESULTS: Ca(2+) imaging revealed that pacemaker activity in human ICC-MY can entrain ICC-SEP to excite CM bundles. Unlike the heart, pacemaker activity in ICC-MY varied in amplitude, propagation distance, and direction, leading to a sporadic activation of ICC-SEP. CONCLUSIONS: ICC-SEP form a crucial conduction pathway for spreading excitation deep into muscle bundles of the human jejunum, necessary for motor patterns underlying mixing. A loss of these cells could severely affect motor activity. |
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Keywords: | CM circular muscle FOV field of view ICC-MY myenteric interstitial cells of Cajal ICC-SEP septal interstitial cells of Cajal LM longitudinal muscle ROI region of interest ST spatiotemporal |
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