Functional Role Of Non-selective Cation Channels On Colonic Excitability In Physiological And Pathological Conditions

Abstract

Integrity of smooth muscle mechanisms is essential for maintaining colonic excitability. This excitability is regulated in part, by the activity of specific ion channels that can affect the resting membrane potential. The experiments performed in this thesis investigated multiple aspects of colonic excitability in various species (human, monkey and mouse) including activity of specific ion channels, their molecular candidates and the regulation of these ion channels in physiological and pathological conditions. Since the resting membrane potential is generally more positive than Ek in gastrointestinal smooth muscle, firstly we hypothesized that non-selective cation channels are involved in setting the resting membrane potential. Secondly we examined intracellular signaling mechanisms of non-selective cation channels that contribute to membrane excitability. Since smooth muscle excitability can be changed in pathological conditions, we also examined the effects of histamine to mimic the acute effects of inflammation in two different species (monkey and mouse). Finally we investigated the functional role of non-selective cation channels in an animal model of colitis.