Seán Ward

Sean Ward


My laboratory is interested in the mechanisms underlying rhythmicity and neuroeffector transmission in visceral organs. Over the last decade we have developed a multi-faceted approach to understand the cell types responsible for the generation of pacemaker activity that leads to phasic contractions of many visceral tissues, especially those of the gastrointestinal tract. We have also increased our understanding of how motor nerve terminals communicate with smooth muscle cells in visceral tissues. Morphological, electrophysiological, molecular biological approaches and calcium imaging including the use of several mutant animal models that have disrupted Kit signaling have led us to the conclusions that there are specialized cells within the walls of visceral organs, called Interstitial cells of Cajal (ICCs).

It is now clear that ICCs serve as: (i) pacemaker cells, generating the spontaneous electrical rhythms within the gastrointestinal tract known as slow waves; (ii) a propagation pathway for slow waves in GI muscles so that large areas of the musculature can be entrained to a dominant pacemaker frequency; (iii) mediators of excitatory cholinergic and inhibitory nitrergic neural inputs from the enteric nervous system, and (iv) stretch receptors that modulate membrane potential and electrical slow wave frequency in gastrointestinal muscles.

Examples of different populations of ICC that exist within the GI tract are illustrated in the digital reconstructions of confocal images illustrated below. The loss of ICC that lie within the intermuscular plane of the small intestine (see confocal image on left) leads to a disruption in pacemaker activity and propagation of slow waves in the small intestine. An absence of intramuscular interstitial cells in the stomach (see image on right) leads to a loss of cholinergic and nitrergic neurotransmission of the stomach wall as well as a loss of stretch-dependent responses in the gastric musculature.

The collegial environment within the Department of Physiology and Cell Biology has allowed members of my laboratory to develop ongoing collaborations with many faculty within our Department and other Departments at the University Of Nevada School Of Medicine. These collaborations have led to the multifaceted approach that we have applied to visceral tissues and our rapid understanding of the functional roles of these cells within the gastrointestinal tract and other organs.