Download Considerations on the structures involved in the

Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
Considerations on the structures involved in the control of transmission
mechanism mediated of calcium pulses
ANTONELLA CHEŞCĂ(1), TIM SANDLE(2), GELLERT ATTILA GYURKA(3)
1,3
Department of Basic, Preventive and Clinical Sciences, Faculty of Medicine, „Transilvania” University of Braşov,
Romania
2
Head of Microbiology, BPL, United Kingdom
*Corresponding author
Antonella Chescǎ, Ph.D.
Lecturer MD, Department of Basic, Preventive and Clinical Sciences, Faculty of Medicine, „Transilvania” University
of Braşov, 56 Nicolae Bălcescu Street, 500019, Braşov, Romania; Phone +40268412185,
Email: [email protected]
Keywords. Calcium transport mechanisms, signaling, structures, illness, calcium ions,
physiology
Summary
studies, it is there is a difference between the
actual concentration of calcium ions in
intracellular and extracellular space. This
determines the cellular penetration and
diffusion.
From this perspective, the flux of calcium
ions involved in the activity of intracellular
processes are carried out according to the
principle that involves the penetration of ionic
calcium into the cells, via channels, through
the diffusion process that follows the
concentration gradient direction (Bianchi
et.al., 2004).
The level of calcium ions in the cell, at
abnormal values, is determined by defining it
as a second messenger, serving as a mediator
of external signals involving hormones,
neurotransmitters and growth factors. Here
the calcium ion interferes with the
transmission of stimuli arising from the cell
surface. The external signals are detected up
by receivers connected to the various
translation mechanisms responsible for
increasing the intracellular calcium ion
concentration and combining this with an
intracellular receptor level - troponin C and
calmodulin - by activating a series of
intracellular processes.
This mode of transmission can be
influenced by other secondary messengers
like cAMP or diacylglycerol. These can lead
to an adjustment to the translation
Given the importance of calcium for good
functioning of the body and knowing its
involvement in signaling mechanisms and
intercellular transport (which involves
mechanisms related to the translation of
transmembrane signals), the study outlined
combines theoretical and practical data
relating to the these processes. Theoretical
information is supported by data collected
from medical practice. Here attention is paid
to the body structures involved in pathologies
and changes that have occurred due to
imbalance of calcium ions within different
structures and at the level of cellular
ultrastructure. With the presentation of the
structural components, these bring into
focus various kinds of diseases associated
with calcium ion pulses.
Introduction
According to the current information, the
level of calcium in the body is around 2% of
body weight. Of this total, 99% of calcium is
contained within bone and the remainder in
the body is in the form of calcium ions bound
to the anion or protein. It is known, however,
that some calcium ions are located on the cell
membrane surface. In the context, it is
important to mention that, according to
The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6
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Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
mechanisms, the expulsion of intracellular
calcium ion or causing receptors that serve as
mediators of cation action (Hüser et.al.,
2000).
Moreover, there are cells that react to
depolarization by increasing intracellular
ionic calcium. Here calcium mobilization
processes
are
voltage
dependent
(Krumschnabel et.al., 2014).
It is widely
thought that the main source of calcium ions
at the extracellular level are the sarcoplasmic
reticulum and in the mitochondria.
Calcium ion influx from outside is
balanced by a corresponding outflow. As this
occurs, every cell membrane has a constant
kinetic. Normally, this has implications for
maintaining calcium homeostasis. Studies
have shown how the membrane systems have
an adjustment-set point characteristic, which
is the where the concentration of calcium ions
in the currents entering and those leaving are
in perfect balance. Further studies have shown
that the mitochondrial point of adjustment is
higher compared to the control within the
sarcolemma and sarcoplasmic reticulum
(Levy et.al., 2005).
With the immobilization of ionic calcium
through
voltage-dependent
process,
depolarization of the cell membrane increases
the internal concentration of calcium ions
through the opening of voltage-dependent
calcium channels. These are located at the cell
membrane ((Krumschnabel et.al., 2014).
Calcium channels play an important role in
smooth muscle, synaptic terminals, heart,
adrenal chromaffin cells of, insulinsecretors
cells ((Hüser et.al., 2000).
Calcium ion flow through such ion
channels is modulated by the secondary
messenger cyclic adenosine monophosphate
(cAMP). This increases the possibility for
each channel to be opened when a membrane
depolarization occurs (Fritzen et.al., 2000).
Depolarization causes calcium deposits also
to mobilize. For asset-dependent receptors, it
is assumed that there is an infinite number of
external signals acting through mobilizing
calcium receptor ((Bianchi et.al., 2004).
Maintaining a high concentration of
calcium in the cytosol, as well as the removal
of this ion in the cytosol, may be achieved by
activating and involving calcium ions. Here it
is
the
calcium-calmodulin
(calciummodulated protein) complex that activates
cationic pumps. Calmodulin functions as a
multifunctional
intermediate
messenger
protein. It transduces calcium signals through
the binding of calcium ions. These are then
modified through the interactions with
differing target proteins.
It is important to study the mechanisms of
muscle contraction relating to fibers in
striated muscle tissue. With this it is useful to
note the presence of lactic acid and lactate, as
well as the final product. This is due to
glycolysis evoked changes occuring at the
cellular level, such as the shift from aerobic to
anaerobic in presence of ATP, and oxygen.
Here studies have shown that muscle lactate is
exported to the liver to facilitate clearance.
This indicates a dynamic mobilization and
utilization of lactate during a cycle of muscle
contraction (Park et.al., 2015).
Numerous effects of ionic calcium into the
cell are connected with synergy and
antagonism, with other second messengers.
From
this
standpoint,
cAMP
and
diacylglycerol play an important role in
modulating various aspects especially in
relation to the calcium signal transmission. In
some cells, the modulation of calcium ions
seems the only function of cAMP and
diacylglycerol. Thus in striated muscle
sarcoplasmic reticulum, calcium release from
troponin C causes contraction and calmodulin
release from the fosforilazkinazei, resulting in
stimulation of glycogen degradation. This
results in the energy required striated muscle
contraction (Bowtell et.al., 2007).
In the myocardium, cAMP increases the
calcium current through ion channels. Protein
kinase A, through which phosphorylates
fosfolambanul stimulates calcium from the
sarcoplasmic reticulum pump, thereby follows
contraction. However, phosphorylated cAMP
troponin I and troponin C affinity for calcium
decreases, causing muscle relaxation (Fritzen
et.al., 2000).
Considered to be the result of lack of
oxygen in skeletal muscle contraction,
glycolytic lactate production is formed and it
operates under aerobic conditions. The
concepts of "cell to cell" and "intracellular
lactate transfer" describe the roles of lactate in
The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6
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Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
the development of oxidative reactions and
gluconeogenic substrates as well as in cell
signaling (Yaniv Y et.al., 2005).
Examples of "cell-cell" exchanges includes
exchanges of glycolytic lactate between white
and red fiber-oxidation in a bed of moss
working between skeletal muscles and the
heart; and net lactate release of tissues; and
gluconeogenesis. With these, mitochondria
are involved in setting the necessary slope
density
for
mitochondrial
cells
as
cardiomyocytes (Yaniv Y et.al., 2008).
Measurements observation on working
arteriovenous show differences between
cardiac and skeletal muscle structures.
Nuclear Magnetic Resonance (NMR) spectral
analysis of these tissues shows that lactate is
formed in cells in vivo (Makrecka-Kuka et.al.,
2015).
The intracellular lactate shuttle (ILS) is a
necessary component of the mechanism
described above. Lactate "cell-cell" (CCLS)
as provided in the gap and lactate vascular
network can be retrieved and used in highly
oxidative cells; or skeletal and cardiac muscle
fibers; or hepatocytes. ILS highlights the role
of mitochondrial redox proton creation and
anion lactate showing slopes needed to
eliminate oxidative mitochondrial reticulum
useful lactate during exercise (Gibala et.al.,
2002). This hypothesis was initially supported
by direct measurement of the lactate oxidation
in isolated mitochondria and conclusions
regarding the existence of mitochondrial
monocarboxylate transporters (mMCT) and
lactate dehydrogenase (mLDH) were drawn.
Subsequently, the presence of complex
mitochondrial lactate oxidation (composed of
mMCT1, CD147 (basigin) mLDH, and
cytochrome oxidase (COX)) was discovered
and shown to have a role in supporting the
presence of ILS (Gnaiger, 2009). Lactate is
capable of upregulating MCT1 and COX gene
and protein expression (Brooks, 2002).
The findings present allow us to
understand how lactate production during
exercise is a physiological signal to activate a
vast network of transcription, affecting MCT1
protein expression and biogenesis of
mitochondrial. This explains how exercise
enhances the ability lactate clearance by
oxidation (Hashimoto
et.al., 2008).
According to some studies, it has been
observed that sepsis and septic shock are
associated with hyperlactatemia (sepsisassociated hyperlactataemia (SAHL)). SAHL
is a strong independent predictor of mortality
and the presence and progression is highly
valued by physicians in order to define a very
high-risk population. Furthermore, laboratory
applications have shown that SAHL is a
marker of tissue hypoxia (Garcia-Alvarez
et.al., 2014).
Issues involving ionic calcium and other
compounds acts as biopharmaceutical
mechanisms and biomolecular signals of
diseases. Thus modicările ultrastructural
cellular results of transmembrane transport
involving calcium and the systems of cell
signaling, can be found in studies using
randomized, double-blind, sets of patients;
and these correlate with disease patterns
(Donnino et.al., 2015).
Materials and methods
In the context of the calcium mechanism
involving transmembrane transport and
cellular signaling, this paper
presents
structures of the modifications of calcium in
the body. The structures presented are from
bodies involved in pathologies. Here it is
noted that striated muscle plays an important
role as an energy producer in the form of
ATP. Cardiac muscle is also influenced by
regulating calcium proper functionality.
Changes in calcium concentration has
consequences for the functionality of the heart
and blood vessels. Also, in the context of
good functionality of the heart ,pathologies
related to imbalances seriously affect organs
such as the liver, which is a manufacturer of
calcium in the form of ATP.
From microscopic preparations we can
observe
structural
details
such
as
mitochondria in binucleate hepatocytes.
Given that the diseases that affect internal
organs in the context of this paper,
preparations of smooth muscle are presented.
Here it is noted that with the uterine smooth
muscle it is important to have a level of
The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6
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Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
optimal calcium necessary for optimal
contractions, especially during labor. With the
analysis of microscopic preparations these
were prepared using conventional histological
techniques and using typical and special
stains. Microscopic preparations were
examined using objective x10 and x40
magnifying power and Nikon microscopes.
Results and discussions
Fig.2. Striated muscle tissue Ferric Hematoxylin
Heidenhein Staining x20, Longitudinal section.
The data presented thus far is associated with
theoretical information. In order to show
physiological effects, outlined below are
played structural images of organs involved in
calcium transport mechanisms, storage and
filing, for the cation.
The first figure presented restores the
structural skeletal muscle fibers. Striated
muscle that is the subject of exercise and the
relaxation mechanism of contraction, releases
lactate or lactic acid following the cessation
of the exercise. In addition to the numerous
mitochondria is striated muscle, which
produces energy in the form of the transporter
adenosine triphosphate (figure 1).
Figure three is of the uterus, showing the
structural, functional and timing of specific
glands and the myometrium, where muscle
fibers are shown with a characteristic
appearance. (figure 3)
Fig.3. Uterus. H&E Staining x20.
section.
Longitudinal
Figure four displays the structural aspect of
the heart, where the cardiac muscle tissue
with a specific type of striated scalariform
disc Eberth, interleaves. (figure 4)
Fig.1. Striated muscle tissue H&E Staining x20.
Longitudinal section.
Skeletal muscle fibers are also shown in
the second figure, in longitudinal section,
using Heidenhein staining, a trichrome stain.
(figure 2)
The Romanian Society for Cell Biology ©, Annals of R. S. C. B., Vol. XXI, Issue 1, 2016, Antonella Cheşcă, pp. 1 – 6
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Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
Fig. 4. Heart. H&E Staining x20. Longitudinal section.
Fig. 6. Liver. Silver impregnation, Gomori Staining
x20. Longitudinal section.
The following figure shows, in detail,
binucleate hepatocytes cords and visible
points of mitochondria throughout the
cytoplasm. Hepatocytes constitute around 7085% of the liver's mass. The liver is an organ
within which energy is stored in the form of
the nucleoside adenosine triphosphate (ATP).
In this context, mitochondria play an
important role in this energy retentive
process. (figure 5)
Knowing that the mechanisms described in
the introduction are reflected on vascular
structures or the artery and vein, the following
figure shows the two types of blood vessels.
The observation is concerned with the
structural difference. The issues presented are
comparable to the skeletal muscles and other
organs involved in the mechanism described
in the introduction of this paper. (figure 7)
Fig. 5. Liver. H&E Staining x20. Longitudinal section.
Fig.7. Liver.
Goldner
Longitudinal section.
The structural appearance of the liver as a
whole is shown in the figure below, using a
special color suggestive. Here it can be
observed, both hepatocytes cords and
elements of the Kiernan space, the
interlobular space in the liver. (figure 6)
Szekely Staining
x20.
Conclusions
The importance of the contribution of this
study has been to explore the interaction of
calcium ions on the proper functions of the
body. Most notably this is through the
involvement of calcium ions with intracellular
transport mechanisms and control of the
transmembrane
role
in
translating
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Annals of R.S.C.B., Vol. XXI, Issue 1, 2016, pp. 1 – 6
Received 12 January 2016; accepted 21 December 2016.
doi: 10.ANN/RSCB-2016-0001:RSCB
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transmembrane signals. Studies are ongoing
to ascertain these functions in more detail.
In the context of the structural issues
presented, this study could be continued and
extended using modern biomolecular analysis.
This would allow further exploration of the
important issues raised.
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