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Am J Physiol Cell Physiol (October 17, 2007). doi:10.1152/ajpcell.00303.2007
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Submitted on July 19, 2007
Accepted on October 13, 2007

Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program

Keith Nehrke1*, Jerod S. Denton2, and William Mowrey3

1 Medicine, University of Rochester Medical Center, Rochester, New York, United States
2 Anesthesiology and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, United States
3 Center for Aging and Developmental Biology, University of Rochester Medical Center, Rochester, New York, United States

* To whom correspondence should be addressed. E-mail: keith_nehrke{at}urmc.rochester.edu.

Defecation in the nematode worm Caenorhabditis elegans is a highly rhythmic behavior that is regulated by a Ca2+ wave generated in the twenty epithelial cells of the intestine, in part through activation of the inositol 1,4,5-trisphosphate receptor (IP3R). Execution of the defecation motor program (DMP) can be modified by external cues such as nutrient availability or mechanical stimulation. To address the likelihood that environmental regulation of the DMP requires integrating distinct cellular and organismal processes, we have developed a method for studying coordinate Ca2+ oscillations and defecation behavior in intact, freely behaving animals. We tested this technique by examining how mutations in genes know to alter Ca2+ handling (including egl-8/PLC{beta}, kqt-3/KCNQ1, sca-1/SERCA, and unc-43/CaMKII) contribute to shaping the Ca2+ wave and asked how Ca2+ wave dynamics in the mutant backgrounds altered execution of the DMP. Notably, we find that Ca2+ waves in the absence of PLC{beta} initiate ectopically, often traveling in reverse, and fail to trigger a complete DMP. These results suggest that the normal supremacy of the posterior intestinal cells is not obligatory for Ca2+ wave occurrence, but instead helps to coordinate the DMP. Furthermore, we present evidence suggesting that an underlying pacemaker appears to oscillate at a faster frequency than the defecation cycle and that arrhythmia may result from uncoupling the pacemaker from the DMP, rather than from disrupting the pacemaker itself. We also show that chronic elevations in Ca2+ have limited influence on the defecation period, but instead alter the interval between successive steps of the DMP. Finally, our results demonstrate that it is possible to assess Ca2+ dynamics and muscular contractions in a completely unrestrained model organism.




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E. Allman, D. Johnson, and K. Nehrke
Loss of the apical V-ATPase a-subunit VHA-6 prevents acidification of the intestinal lumen during a rhythmic behavior in C. elegans
Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1071 - C1081.
[Abstract] [Full Text] [PDF]




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