Functional Role Of Non-selective Cation Channels On Colonic Excitability In Physiological And Pathological Conditions
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Authors
Dwyer, Laura
Issue Date
2009
Type
Dissertation
Language
Keywords
HISTAMINE , INFLAMMATION , NON-SELECTIVE CATION CHANNELS , RESTING MEMBRANE POTENTIAL
Alternative Title
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.
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In Copyright(All Rights Reserved)