MECHANOTRANSDUCTION IN INTESTINAL SMOOTH MUSCLE CELLS

Project: Research project

Project Details

Description

Mechano-gated ion channels provide a mechanism for cells to respond
directly to changes in their environment and are involved in several
key cellular functions including cell division, regulation of volume,
muscle tone and muscle.hypertrophy. Neurons, cardiac, and vascular
smooth muscle cells have mechano-gated ion channels. However, the
presence and significance of mechano-gated ion channels in
gastrointestinal smooth muscle is unknown. The objective of this
proposal is to establish the physiological importance of mechano-gated
ion channels in single human and canine jejunal circular smooth muscle
cells. The Preliminary data obtained by the PI suggest that membrane
stretch, increase in cell volume, and cytoskeletal manipulation
modulate the whole cell current in human and canine jejunal circular
smooth muscle cells. Based on these preliminary data the working
hypothesis of this proposal is that mechano-gated ion channels are
present on smooth muscle cells and that activation of the channels
results in changes in ionic flux and membrane potential, ultimately
resulting in changes in intestinal contractility. There are three
specific aims: (1) to determine if a change in shape or size of human
and canine jejunal circular smooth muscle cells activates mechano-gated
channels; (2) to determine which ion channel or channels underlies the
increase in whole cell current evoked by a change in cell size or
shape; and (3), to determine if regulation of mechano-gated ion channel
open probability is dependent on the cellular cytoskeleton. The
development of a dissociation technique for obtaining healthy human
small intestinal smooth muscle cells by the PI will enable the use of
patch clamp recordings and immunofluorescent techniques to address the
three specific aims. The demonstration of mechano-gated ion channels
in gastrointestinal smooth muscle will provide a novel pathway by which
small intestinal smooth muscle cells can directly and appropriately
respond to changes in their environment. Activation of mechano-gated
ion channels may be of physiological significance in the smooth muscle
response to changes in intraluminal pressure in normal digestion, and
of pathophysiological significance in inflammatory or obstructive
diseases such as Crohn's disease and strictures and in irritable bowel
syndrome where mechano-gated ion channels may be overexpressed.
StatusFinished
Effective start/end date9/1/978/31/16

ASJC

  • Medicine(all)