4. DEFINITION
The activity produced in an organ, tissue, or part, such as a nerve cell, as a
result of stimulation.
The cells get excitated through signals sent by the nervous system
The signals may be chemical or electrical
Electrical signals are seen mostly in lower group of organisms where as
chemical signals are seen in the higher group of organisms
The signals transmitted by the nervous system are transmitted through the
nerve cells called NEURONS
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5. A neuron
A neuron:
Nerve cell
Trasmits signals in the form of
action potential.
Parts:
The cell body (soma or);
The dendrites,
Receive information from
other neurons
Axon, which conducts electrical
impulses away from the cell body.
Terminal buttons
( terminal knobs, boutons, end-feet,
or synaptic knobs)
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7. Synapse
The junction between the axon terminals of a
neuron and the receiving cell is called a synapse.
7
8. Synapse
Components of synapse:
Pre-synaptic neuron : the neuron that secretes the
transmitter substance.
Postsynaptic neuron: the neuron on which the transmitter
acts.
Synaptic cleft: The space that seperates the pre-synaptic
terminal from the postsynaptic neuron.
Neuromuscular Junction ( NMJ):
Pre-synaptic neuron: Motor neuron
Post synaptic: Muscle cell.
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10. Synapse
The pre-synaptic
neuron contains:
The transmitter
vesicles
The transmitter
vesicles contain the
transmitter substance
that, when released
into the synaptic cleft
called
neurotransmitters.
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11. Neurotransmitters.
A chemical substance secreted by a nerve
ending into the synapse.
Acts on receptor proteins in the membrane
of the next neuron to excite the neuron,
inhibit it, or modify its function.
E.g.
Acetylcholine,
Norepinephrine,
Epinephrine,Gamma-aminobutyric acid (GABA),
Glycine
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13. NEUROHUMORAL TRANSMISSION
It is the process in which an impulse is transmitted
between the presynaptic & postsynaptic neuron by means
of neurohumoral mediator signals resulting in
enhancement or inhibition of the response
The nerve cells transmit their messages across the
synapse by releasing chemical mediators from nerve
ending into the synaptic cleft
Influx of Ca ions during nerve impulse releases the
neurotransmitter from synaptic vesicles of the presynaptic
nerve into the synaptic cleft that reach the postsynaptic
receptor site & exert their action
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15. 1) Conduction of impulse or action potential
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axon
• inside
• outside
K+ ions
• high
• low
Na & Cl ions
• low
• high
16. The membrane potential of the axon is -70mV
The conc. Of these ions is maintained by Na-K pump
Once the action potential reaches the presynaptic nerve fibres Na
permeability is increased hence Na moves in causing depolarization
The membrane potential is +20mV
Depolarization also opens K channels causing its efflux
This concentration of ions is brought to normal by Na-K pump which
pumps 3 Na ions out & 2 K ions in bringing the potential back to
normal
During this process the ionic currents are generated that activate the
channels present on the adjacent neurons
16
17. 2) Release of neurotransmitter
The neurotransmitters are formed in the nerve terminals
& stored in synaptic vesicles of the synaptic bulb
Once the action potential reaches the presynaptic nerve
fibres it activates the Ca channels present in the nerve
terminals
The intraterminal Ca level increases causing the snaptic
vesicles to fuse with the axon which causes the
neurotransmitters to release into the synaptic cleft by a
process called as exocytosis
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18. 3) Interaction of the neurotransmitter
The neurotransmitters released into the synapse join the
post junctional receptors present on the postsynaptic
nerve & exert their action either EXCITATORY or
INHIBITORY
RESPONSES ARE OF TWO TYPES
EXCITATORY POSTSYNAPTIC POTENTIAL(EPSP)
INHIBITORY POSTSYNAPTIC POTENTIAL(IPSP)
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19. EXCITATORY POSTSYNAPTIC POTENTIAL(EPSP)
In EPSP the permeability of axonal membrane to all
cations (Na K Ca) is enhanced
Na & Ca move inside the membrane causing depolarization
K ions move out
EPSP occurs only when the neurotransmitter is ASPARTATE
or GLUTAMATE
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20. INHIBITORY POSTSYNAPTIC POTENTIAL(IPSP)
In IPSP the axonal permeability to K & Cl ions is enhance
IPSP involves influx of Cl ions & efflux of K ions
IPSP occurs only when the neurotransmiters are either
glycine or GABA
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21. 4)TERMINATION of neurotransmitter
It can occur by either combining with certain
receptors on the postsynaptic membrane as in the
case with adrenoreceptor binding drugs ex;
noradrenaline
Or it may get inactivaetd by certain enzymes
present at the receptor site as in the case with
Ach
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26. TYPES
An isometric contraction of a muscle generates tension without changing
length
In isotonic contraction, the tension in the muscle remains constant despite a
change in muscle length. This can occur only when a muscle's maximal force
of contraction exceeds the total load on the muscle.
In concentric contraction, muscle tension is sufficient to overcome the load,
and the muscle shortens as it contracts. This occurs when the force generated
by the muscle exceeds the load opposing its contraction.
In eccentric contraction, the tension generated is insufficient to overcome
the external load on the muscle and the muscle fibers lengthen as they
contract
Eccentric contractions normally occur as a braking force in opposition to a
concentric contraction to protect joints from damage.
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27. PHYSIOLOGY
For voluntary muscles, all contraction (excluding reflexes) occurs as a
result of conscious effort originating in the brain. The brain sends
signals, in the form of action potentials, through the nervous
system to the motor neuron that innervates several muscle fibers
Involuntary muscles such as the heart or smooth muscles in the gut
and vascular system contract as a result of non-conscious brain
activity or stimuli endogenous to the muscle itself
There are three general types of muscle tissues
Skeletal muscle responsible for movement
Cardiac muscle responsible for pumping blood
Smooth muscle responsible for sustained contractions in the vascular
system, gastrointestinal tract, and other areas in the body.
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29. EXCITATION-CONTRACTION COUPLING
The membrane potential of a skeletal muscle cell is depolarized by an action
potential
This depolarisation activates non-gated voltage sensors,
DHPRs(dihydropyridine receptors The Ca release channels)
This activates RyR(the ryanodine receptor i.e voltage-gated L-type calcium
channels ) type 1 via foot processes (involving conformational changes that
allosterically activates the RyRs)
As the RyRs open, calcium is released from the SR into the local junctional
space, which then diffuses into the bulk cytoplasm to cause a calcium spark
The near synchronous activation of thousands of calcium sparks by the action
potential causes a cell wide increase in calcium giving rise to the upstroke of
the calcium transient.
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30. The calcium released into the cytosol binds to Troponin C by the actin
filaments, to allow cross-bridge cycling, producing force and, in some
situations, motion
The sarco/endoplasmic reticulum calcium-ATPase (SERCA) actively pumps
calcium back into the SR
As calcium declines back to resting levels, the force declines and relaxation
occurs
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31. SLIDING FILAMENT THEORY
The sliding filament theory describes a process used by muscles to contract. It
is a cycle of repetitive events that cause a thin filament to slide over a thick
filament and generate tension in the muscle. It was independently developed
by Andrew F. Huxley and Rolf Niedergerke and by Hugh Huxley and Jean
Hanson in 1954.
When a muscle cell contracts, the thin filaments slide past the thick filaments,
and the sarcomere shortens. This process comprised of several steps is called
the Sliding Filament Theory. It is also called the Walk Along Theory or the
Ratchet Theory
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33. STEPS INVOLVED
Before contraction begins, An ATP molecule binds to the
myosin head of the cross-bridges.
The ATPase activity of the myosin head immediately
cleaves the ATP molecule but the products (ADP+P)
remains bound to the head. Now the myosin head is in a
high energy state and ready to bind to the actin molecule.
When the troponin-tropomyosin complex binds with
calcium ions that come from the sarcoplasmic reticulum,
it pulls the tropomyosin so that the active sites on the
actin filaments for the attachment of the myosin molecule
are uncovered.
Myosin head binds to the active site on the actin
molecule.
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34. The bond b/w the head of the cross bridges(myosin) &
the actin filaments causes a the bridge to change shape
bending 45° inwards as if it was on a hinge, stroking
towards the centre of the sarcomere, like the stroking of
a boat oar. This is called a POWER STROKE.
This power stroke pulls the thin filament inward only a
small distance.
Once the head tilts, this allows release of ADP &
phosphate ions.
At the site of release of ADP, a new ATP binds. This
binding causes the detachment of the myosin head
from the actin.
34
35. A new cycle of attachment-detachment-attachment begins.
Repeated cycles of cross-bridge binding, bending and detachment
complete
the shortening and contraction of the muscle.
35
36. After the ATP has bound to the myosin head, the
binding of Myosin to Actin molecule takes place:
36
37. Once the actin active sites are
uncovered, the myosin binds to it:
37
40. Shortening of the Muscle:
• The thick and thin filaments
DO NOT shorten.
• Contraction is accomplished
by the thin filaments from
opposite sides of each
sarcomere sliding closer
together or overlapping the
thick filaments further.
• The H-zone becomes smaller
as the thin filaments
approach each other.
• The I band becomes smaller
as the thin filaments further
overlap the thick filaments.
• The width of the A band
remains unchanged as it
depends on the thick
filaments and the thick
filaments do not change
length.
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41. CONTRACTION IN CARDIAC MUSCLES
Cardiac muscle fibers contract via excitation-contraction coupling, using a
mechanism unique to cardiac muscle called calcium-induced calcium
release.
Excitation-contraction coupling describes the process of converting an
electrical stimulus into a mechanical response.
Calcium-induced calcium release involves the conduction of
calcium ions into the cardiomyocyte, triggering further release of ions
into the cytoplasm.
Contraction in cardiac muscle follows the sliding filament model of
contraction.
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42. 1)excitation contraction coupling (ECC)
The physiological process of converting an electrical
stimulus to a mechanical response.
2)calcium-induced calcium release (CICR)
A process whereby calcium can trigger release of further
calcium from the muscle sarcoplasmic reticulum.
3)T-tubule
Deep invagination of the sarcolemma, which is the plasma
membrane, only found in skeletal and cardiac muscle
cells.
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43. Cardiomyocytes are capable of coordinated contraction,
controlled through intercalated discs. The IDs
spread action potentials to support the synchronized
contraction of the myocardium. In cardiac, skeletal, and
some smooth muscle tissue, contraction occurs through a
phenomenon known as excitation contraction coupling
(ECC). ECC describes the process of converting an
electrical stimulus from the neurons into a mechanical
response. In muscle tissue, the electrical stimulus is an
action potential and the desired mechanical response is
contraction.
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44. In cardiac muscle, ECC is dependent on a phenomenon called
calcium-induced calcium release (CICR), which involves the
conduction of calcium ions into the cell triggering further
release of ions into the cytoplasm. Like skeletal muscle, the
initiation and upshoot of the action potential in ventricular
muscle cells is derived from the entry of sodium ions across the
sarcolemma in a regenerative process. However, in cardiac
muscle, an inward flux of extracellular calcium ions through
calcium channels on theT-tubules sustains the depolarization of
cardiac muscle cells for a longer duration.
Contraction in cardiac muscle occurs via the sliding filament
model of contraction . In the sliding filament
model, myosin filaments slide along actin filaments to shorten
or lengthen the muscle fiber for contraction and relaxation.
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45. The pathway of contraction can be described
in five steps:
An action potential, induced by pacemaker cells, is conducted to contractile
cardiomyocytes through IDs, specifically gap junctions.
As the action potential travels between sarcomeres, it activates the calcium
channels in the T-tubules, resulting in an influx of calcium ions into the cell.
Calcium in the cytoplasm then binds to cardiac troponin-C, which moves the
troponin complex away from the actin binding site. This removal of the troponin
complex frees the actin to be bound by myosin and initiates contraction.
The myosin head pulls the actin filament toward the center of the sarcomere,
contracting the muscle.
Intracellular calcium is then removed by the sarcoplasmic reticulum, dropping
intracellular calcium concentration, returning the troponin complex to its
inhibiting position on the active site of actin, and effectively ending contraction
45
46. This animation shows myosin filaments (red)
sliding along the actin filaments (pink) to
contract a muscle cell.
46
49. DEFINITION
Secretion is the process of elaborating, releasing, and
oozing chemicals, or a secreted chemical substance from
a cell or gland.
In contrast to excretion, the substance may have a certain function,
rather than being a waste product.
The classical mechanism of cell secretion is via secretory portals at
the cell plasma membrane called porosomes.
Porosomes are permanent cup-shaped lipoprotein structure at the cell
plasma membrane, where secretory vesicles transiently dock and fuse
to release intra-vesicular contents from the cell.
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51. MECHANISM
The proteins to be secreated are synthesised in the
ribosomes & translocated into the rough ER lumen where
they get glycosylated & the molecular chaperones aid
protein folding
Misfolded proteins are usually identified here and
retrotranslocated by ER-associated degradation to
the cytosol, where they are degraded by a proteasome.
The vesicles containing the properly folded proteins then
enter the Golgi apparatus.
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52. In the Golgi apparatus, the glycosylation of the proteins is
modified and further posttranslational modifications,
including cleavage and functionalization, may occur.
The proteins are then moved into secretory vesicles which
travel along the cytoskeleton to the edge of the cell. More
modification can occur in the secretory vesicles (for
example insulin is cleaved from proinsulin in the secretory
vesicles).
Eventually, there is vesicle fusion with the cell
membrane at a structure called the porosome, in a
process called exocytosis, dumping its contents out of the
cell's environment
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54. NON CLASSICAL MECHANISMS
There are many proteins
like FGF1 (aFGF), FGF2 (bFGF), interleukin-1 (IL1) etc.
which do not have a signal sequence. They do not use the
classical ER-golgi pathway. These are secreted through
various nonclassical pathways.
At least four nonclassical (unconventional) protein
secretion pathways have been described. They include 1)
direct translocation of proteins across the plasma
membrane likely through membrane transporters, 2)
blebbing, 3) lysosomal secretion, and 4) release via
exosomes derived from multivesicular bodies
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55. Blebbing
In cell biology, a bleb is a protrusion, or bulge, of the plasma
membrane of a cell, caused by localized decoupling of
the cytoskeleton from the plasma membrane. Blebbing or zeiosis is
the formation of blebs.
During apoptosis (programmed cell death), the cell's cytoskeleton
breaks up and causes the membrane to bulge outward.[5] These bulges
may separate from the cell, taking a portion of cytoplasm with them,
to become known as apoptotic bodies. Phagocytic cells eventually
consume these fragments and the components are recycled.
Blebbing also has important functions in other cellular processes,
including cell locomotion, cell division, and physical or chemical
stresses.
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