2 research outputs found
Mathematical modelling and analysis of calcium oscillations in excitable and non-excitable cell lines
Information is transmitted from the cell surface to various specific targets in the cell via several cellular signaling pathways. Cytosolic free calcium (Ca2+)is one of
the most versatile and ubiquitous intracellular messengers since it is able to regulate
diverse number of functions such as proliferation, secretion, fertilization, metabolism,
learning and memory. In the last couple of years, evidence has been accumulating
that Ca2+ ion is able to integrate information from multiple signaling pathways and
convert this information into a code which regulates events ranging from contraction
to modification of gene expression (Berridge et al. 1998). It was shown that Ca2+
concentration displays oscillatory behavior in response to agonist stimulation in a
variety of cells(Goldbeter 1996) and the frequency of these oscillations increases with
the concentration of agonist, a behavior called frequency encoding which has led to the
concept that many Ca2+-regulated processes are controlled by these codes(Berridge
1998).
Although the presence of Ca2+ oscillations and the sources of Ca2+ pools involved
is known in many cell types, it is yet not known how the various frequencies of
Ca2+ oscillations are converted into codes that regulate the numerous cellular events.
Recently a number of cellular targets that decode Ca2+ signals and are tuned to
the frequency of Ca2+ oscillations have been identified. Prominent among them are calcium-calmodulin kinase II (CAM II) and protein kinase C (PKC).
The objective of this work is to study and mathematically model the oxytocin
and vasopressin-induced Ca2+ oscillations in cells of normal rat liver (Clone 9) and
cells of pregnant human myometrium. The proposed model accounts for the receptor-controlled
Ca2+ oscillations involving positive feedback leading to activation of phospholipase
C (PLC) and negative feedback from PKC onto G-proteins which simulates
many of the features of observed intracellular Ca2+. The model also incorporates
the concept that coordinated Ca2+ signals in a group of hepatocytes require both
effective gap junctions and the presence of agonist at each cell surface. Another objective
of this research is to understand the relevance of frequency-encoded signals
by performing an analysis of frequencies of Ca2+ oscillations using the Fast Fourier
Transform and the Wavelet Transform. The validity of the model was confirmed by
using statistical tests to check if the frequencies and amplitudes of the experimental
Ca2+ oscillations match with those of the modelled oscillations
Remodeling of fiber and laminar architecture of rat heart septum in a transitional normal state between pressure overload hypertrophy and failure
Congestive Heart Failure (CHF) is a major fatal disease today in the United
States. The heart's function is a mechanical one. To diagnose and treat CHF effectively
there is a need to understand at the microstructural level, the differences in
the response of the myocardium to a change in its mechanical environment. Hence to
assess growth and remodeling processes in the myocardium, the fiber and myolaminar
structure of two groups of Dahl salt-sensitive rats were compared: low salt (LS)
normal controls and a high salt (HS) group with hearts in "transitional eutrophy"
defined by normal size and shape but in transition from pressure overload hypertrophy
to dilated hypertrophy. To create the HS group with transitional eutrophy, we
fed Dahl salt-sensitive rats, a sustained high salt diet from age 6 wks till sacrifice
at age 11-13 wks. Such rats have a heart that transitions from too thick (pressure
overload hypertrophy at about age 9 wks) to too thin (dilated hypertrophy at about
age 15 wks to death) with a transitional period (age 11-13 wks) having normal size
and shape. Fiber angles, sheet angles, number and thickness of sheets were measured
in the septum at four transmural quarters (TQ1 to TQ4 with TQ1 being closest to
LV and TQ4 closest to RV). A uniformity index was defined to characterize sheet
angle dispersion. Upon comparison to LS controls, the HS group had normal size hearts with normal shape. However, there was a significant increase in the number
of sheets, which corresponded with a significant decrease in the thickness of sheets in
all quarters in HS group. Differences in fiber angles were significant in TQ1, TQ2,
and TQ4 with fiber angles more positive in HS group. Differences in sheet angles
and uniformity index were not significant. Despite having a normal size and shape,
we found that hearts in a state of transitional eutrophy have a significantly different
fiber and sheet morphology.
The experimental data was used to develop a model that represents the path to
failure that may be taken by the myolaminae when the heart is subjected to excessive
pressure overload