Biomedical Engineering Reference
In-Depth Information
reduces the tension at the membrane-water interface, and reduces the lateral pressure
profile close to the membrane-water interface. This supports the hypothesis that anes-
thetics may act by changing the lateral pressure profile exerted on proteins embedded
in membranes. A later study [ 20 ] using the anesthetic drug (R)-(-)-ketamine also pro-
vides evidence for a lateral pressure-mediated mode of anesthesia. The effects of the
membrane's lateral pressure profile on the integral membrane protein functions are
well-addressed using some test model cases discussed in Chap. 5 .
Another study [ 16 ] suggests that ethanol induces expansion of the membrane,
accompanied by a drop in the membrane thickness, as well as disordering and
enhanced inter-digitation of lipid acyl chains. These changes become more pro-
nounced with increases in ethanol concentration, but the bilayer structure of the
membrane is maintained as long as the ethanol concentration is not too high. How-
ever, due to the effects of extremely high ethanol concentration, even a non-bilayer
phase can be achieved.
7.5 Cystic Fibrosis Transmembrane Conductance Regulator
Ion channels play an important role in human physiology. Different ions are used for
various functions in various organs of the body. The human body employs different
ion channels to secrete ions and maintain concentrations in fluids outside and inside
the cells. For example, cystic fibrosis transmembrane conductance regulator (CFTR)
is highly expressed in the pancreatic ductal epithelium. It plays an important role in
ductal bicarbonate ion secretions. Furthermore, the thickness of mucus produced in
the bronchi is controlled via the secretion or the absorption of ions by the alveoli
cells. However, pathological changes to these ion channels lead to an imbalance. For
example, the cell may become too tight, causing a shutdown of ion flow, as is the case
in a disease referred to as cystic fibrosis. On the other hand, the cells may become
too leaky, for example when a person falls sick due to flu or cold. This makes it very
important to study the properties of various ion channels, and their interactions with
each other in a cellular layer as well as the pathways taken by different ions.
Horisberger [ 26 ] developed the original quantitiative model of the epithelial
sodium channels (ENaC) and the CFTR. ENaC-CFTR interactions were described
including the role of electrical coupling of ion fluxes explored in an epithelial cell
model involving ion transport across a layer of epithelial cells, aimed at explain-
ing how effects in one channel would affect the other. The model employed different
types of ion channels. The first type of channels employed by the model were passive
transporters. These do not require energy input, i.e. adenosine triphosphate (ATP),
since they transport ions along the concentration or charge gradient. Some of the
prominent ion channels that fit this category are ENaC and CFTR. Figure 7.5 shows
a general model of such a pathway.
The second type of ion transporter employed by the Horisberger model is an active
pump. It uses ATP to pump three Na + ions outside the cell and two K + ions inside
the cell against the concentration gradient. This is the only active transporter in the
 
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