Septal interstitial cells of Cajal conduct pacemaker activity to excite muscle bundles in human jejunum.
OBJECTIVE
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.
Department of Physiology & Cell Biology, University of Nevada School of Medicine, Reno, Nevada 89557, USA.
Hyun-Tai
HT
Lee
Grant W
GW
Hennig
Neal W
NW
Fleming
Kathleen D
KD
Keef
Nick J
NJ
Spencer
Sean M
SM
Ward
Kenton M
KM
Sanders
Terence K
TK
Smith
D000328:Adult; D001683:Biological Clocks / Q000502:physiology*; D004594:Electrophysiology; D005260:Female; D005769:Gastrointestinal Motility / Q000502:physiology; D006801:Humans; D007583:Jejunum / Q000166:cytology* / Q000294:innervation* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology; D009197:Myenteric Plexus / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*