The aim of this project continues to the elucidation of certain mechanisms involved in the coordination of intestinal motility. One of the major myogenic factors involve in such coordination is the intestinal slow wave (SW). Studies will be directed at elucidating several properties of SW's generated by the cat intestine, including (1) their cellular origin, (2) the mechanism underlying SW depolarization, (3) their mode of interaction, and (4) the decrease in SW propagation velocity along the intestine under normal physiological conditions and following intestinal transection and anastomosis. (1) and (2) will be studied by recording from cells in the longitudinal and circular muscle layers after electrically uncoupling the cells by exposure to 3.5 mM heptanol. Tissue impedance studies show that this concentration of heptanol completely and reversibly uncouples cells of both muscle layers. Other studies show that this concentration of heptanol does not alter membrane resistance and has negligible effects on spike potential amplitude and dV/dt. Electrically isolated cells which generate SW's will be considered pacemaker cells. Measurement of membrane resistance in such cells will indicate whether or not SW depolarization is associated with increased membrane conductance. (3) will be studied by recording from longitudinal muscle cells on either side of a heptanol gap, while electrically entraining SW's on one side of the gap. It is anticipated that increasing the junctional resistance of the muscle cells in the gap will result in loss of entrainment distal to the gap, the development of waxing and waning, and eventually complete dissociation, indicating the importance of low resistance coupling for entrainment. (4) will be studied by measuring pertinent electrical parameters of cells in the upper and lower small intestine in an attempt to quantitatively describe SW propagation in terms of cable theory. Related studies will be undertaken in an attempt to determine if the decrease in SW propagation velocity distal to an intestinal transection and anastomosis is due to prolongation of the refractory period resulting from protracted reduction in SW frequency. These studies will provide basic information regarding myogenic mechanisms which coordinate intestinal motility under normal conditions, and following intestinal transection and anastomosis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK006958-19A3
Application #
3224495
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1976-01-01
Project End
1990-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
19
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Upstate Medical University
Department
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Bortoff, A; Terasaka, D (1990) Changes in intestinal slow wave propagation velocity during the estrus cycle in the cat. Prog Clin Biol Res 327:351-9
Terasaka, D; Bortoff, A; Sillin, L F (1989) Postprandial changes in intestinal slow-wave propagation reflect a decrease in cell coupling. Am J Physiol 257:G463-9