Rhythmicity and Neuroeffector Control of Visceral Smooth Muscle  

Many visceral organs (including the stomach, duodenum, colon, uterus and urethra) display phasic contractions that are necessary for their function.  Our research aim is to understand more fully the specific cell types responsible for, and the mechanisms involved, in the generation of this contractile activity.  We are also interested in how intrinsic and extrinsic motor nerves modulate tone and contractile activity of visceral smooth muscles and how this is altered in pathophysiological conditions. 

In the gastrointestinal tract, specialized populations of cells, known as Interstitial Cells of Cajal (ICC) generate and propagate electrical slow waves which underlie the phasic contractions of the gut wall.  Our studies provided some of the first functional evidence that specific classes of ICC mediate cholinergic and nitrergic neural inputs within the musculature of the stomach.  Evidence is accumulating that ICC may play similar roles in other visceral organs. 

The primary aim of our current research is to identify how rhythmicity, neuroeffector transmission and cell physiology is modified in visceral organs, particularly the gastrointestinal tract, as result of diabetes.   There is growing evidence that impaired gastrointestinal function associated with diabetes can be directly linked to an impaired functioning of interstitial cells of Cajal (ICC). My research goal is to use this knowledge to recover or improve the impaired neural reflexes in the gastrointestinal tract that occur as a consequence of diabetes.

We use a multi-faceted approach including electrophysiological intracellular recordings, isometric tension experiments, immunohistochemistry and molecular biology techniques. To study the pathophysiological effects of diabetes we utilize mice models that develop diabetes as a result of feeding on a high-fat diet (i.e. diet-induced obese C57Bl6) or due to a genetic mutation of the receptor for the satiety factor leptin (i.e. ob/ob and db/db mice).  Morphological and functional experiments are also performed on human gastric tissue specimens obtained from gastric bypass surgeries.