Physiology Flashcards
WHAT IS HOMEOSTASIS
Maintenance of nearly constant conditions in the internal environment.
what is internal environment
extracellular fluid or interstitial fluid
difference between ICF and ECF
ECF
14 L
Large amount of Sodium, chloride and bicabonate ions.
Oxygen and carbon dioxide.
Nutrients: Glucose, fatty acids and amino acids.
ICF
28 L
Potassium, magnesium and phosphate
why is ECF called internal environment
ECF has ions & nutrients needed by the cells to maintain cell life.
All cells live in essentially the same environment (ECF).
ECF = internal environment / milieu interieur
Cell growth & functions depend on proper concentration of components of internal environment (oxygen, glucose, different ions, amino acids, fatty substances etc..
how many times the blood circulate in one minute
At rest:
1 rotation / minute.
Extreme activity:
6 rotations / minute
define feedforward
term used for responses made in anticipation of a change
define feedback and name its type
Refers to responses made after change has been detected
Types of feedback systems
Negative
Positive
what are examples of negative feedback
Higher conc. of CO2 in ECF Increase in pulmonary ventilation more expiration of CO2 decrease in CO2 conc. in ECF.
High blood pressure series of reactions lower pressure OR
Low blood pressure series of reactions higher pressure.
Both the effects are negative to the initiating stimulus.
Thus homeostasis is maintained to prevent excess or deficiency of substances internal environment (ECF) is kept constant.
give example of positive feedback resulting in death
Normal heart pumps 5L/min.
2L Bled person poor pumping, less arterial pressure, less coronary flow weak heart less pumping, further less coronary flow more weak heart death.
Conclusion: Initiating stimulus causes more of the same (positive feed back).
Mild positive feedback may not lead to death, if overcome by negative feedback control (e.g., if person bled 1L Control mechanisms recovery).
describe positive feedback as part of a negative feedback mechanism
Rupture of blood vessel formation of clot activation of clotting factors / enzymes within the clot.
Some of these enzymes activate enzymes of adjacent blood more blood clotting till plugging of hole bleeding stops.
Sometimes unwanted clots formation atherosclerotic plaque in coronary artery acute heart attack.
describe positive feedback mechanism associated with childbirth
Strong uterine contractions during childbirth baby’s head pushed through cervix stretch of cervix signals through uterine muscle body of uterus more powerful contractions more stretch to cervix more stronger contractions.
If strong enough baby is born.
If not strong enough contractions die out restart after few days.
describe and relate feedforward control and adaptive response
When there is not enough time for afferent signals (from periphery to brain) & efferent nerve signals (from brain to periphery) sensory nerve signals from moving parts apprise the brain, whether movement is performed correctly (FEED FORWARD CONTROL)
If not brain corrects feed forward signals in the next attempt of muscle contraction.
If further correction is required done in subsequent contractions (ADAPTIVE CONTROL / DELAYED NEGATIVE FEEDBACK).
describe cytoskeleton nd its components
Cytoskeleton, a system of fibers that not only maintains the structure of the cell but also permits it to change shape and move.
Microtubules
Intermediate filaments
Microfilaments
describe the structure of microtubules in cell
Uniform in size and straight.
25nm in diameter and several micrometers in length.
Wall of microtubules consists of individual filamentous structures made of protein tubulin.
what are the functions of microtubules
They are considered to be a framework that determines the shape of the cell.
They are involved in transport of macromolecules in the cell’s interior.
Several cell organelles are derived from special assemblies of microtubules.
Cilia, flagella, basal bodies and centrioles have groups of microtubules arranged in a special fashion.
Mitotic spindles are also composed of microtubules
describe strcuture and function of microfilaments
Microfilaments represent the active or mobile part of cytoskeleton.
These are the thinnest, ranging in diameter from 6 to 7 nm.
Composed of protein actin, myosin, as well as tropomyosin and other proteins.
Actin filaments are made of globular actin molecules, called G-actin.
They help generate movement (muscle contraction, cell division and cell locomotion) and provide mechanical support to cell.
describe types and function of intermediate filaments
Found in parts of cells subject to mechanical stress, help stabilize the position of organelles such as nucleus & help attach cells to one another.
Keratin filaments, present in epithelial cells.
Neurofilaments, present in axons, dendrites.
Glial filaments, present in astrocyte.
Heterogenous filaments, e.g., desmin and vimentin filaments.
what are the functions of cytoskeleton
Plays an important role in maintaining the cell shape.
Cytoskeletal fibers stabilize the positions of organelles.
Cytoskeleton helps transport materials into the cell and within cytoplasm.
Fibers of cytoskeleton connect with protein fibers in the extracellular space, linking cells to each other and to support material outside the cells.
Cytoskeleton enables cell movement
describe structure and structural components of cilia
Cilia are short, hair like structures projecting from the cell surface like the bristles of brush.
Surface of cilium is continuation of cell membrane, and its core contains nine pairs of microtubules surrounding a central pair.
Multiple protein arms composed of protein dynein, having ATPase activity, project from tubules.
Microtubules terminate just inside the cell at basal body. Or cilium is an outgrowth of basal body.
Basal body is similar in structure to centriole.
what are the functions of cilia
Cilia beat rythmically back and forth
Ciliary movement creates currents that sweep fluids or secretions across the cell surface.
Ciliary movement is a whip like movement that occurs in only 2 places in human body: on the inner surfaces of respiratory airways and on the inner surfaces of uterine tubes (fallopian tubes).
In resp. airways, movement of cilia causes a layer of mucus to move towards pharynx.
In uterine tubes, it moves ovum towards uterus.
what are functions and functional elements of flagellum
Function of flagellum is to push the cell through fluid with wave like movements, just as undulating contractions of a snake’s body.
Axoneme is the term applied to axial structure of cilia and flagella, and is the essential motile element.
There are 2 conditions for continuous beating of axoneme: presence of ATP and appropriate ionic conditions, especially calcium and magnesium
describe ameboid movement
It means movement of an entire cell in relation to its surroundings. For example, movement of WBC’s through tissues.
This movement begins with protrusion of pseudopodium from one end of the cell and attaches to a new area of tissue.
Remaining cell is pulled toward pseudopodium.
what is the mechanism of ameboid movement
It results from formation of new cell membrane continuously at the leading edge of pseudopodium and continuous absorption of membrane in remaining parts of cell.
Attachment of pseudopodium to surrounding tissues occurs while remaining cell is pulled forwards towards the point of attachment.
Attachment is caused by receptors present in exocytotic vesicles.
Vesicles become part of pseudopodial membrane and they open to exterior.
This exposes the receptors which now attach to surrounding tissues.
At the opposite end of cell, receptors pull away from their ligands, forming endocytotic vesicles.
These vesicles move toward pseudopodial end, where they are used to form new membrane for pseudopodium.
Energy is required for all this mechanism.
Protein actin is present in cytoplasm of all cells.
Actin network binds with another protein, myosin thus causing contraction.
Whole process is energized by ATP.
what is the intercellular gap between epithelium and other closely packed tissues
20nm
define cell junctions and their function
Acell junction(orintercellularbridge) is a type of structure that exists within the tissue of some multicellular organisms, such as animals.
Cell junctionsconsist of multiprotein complexes that provide contact between neighboringcellsor between acelland the extracellular matrix
what are the forces that hold cells together
Mutual force of cohesion.
Cell junctions: specialized structural arrangements present at various sites.
describe classification of cell junctions on the basis of shape and contact area
1) Limited extent:
e. g., MACULA (spot / punctate area)
2) Around entire cell:
e. g., ZONULA (belt / girdle like)
describe classification of cell junctions on the basis of relative closeness ad nature of cell contact
1) No intercellular space, cell membranes in contact / fused:
e. g., OCCLUDENS.
2) Intercellular space is 20-25 nm wide & dense granular material in intercellular space & on cytoplasmic surfaces of adjacent cell membranes:
e. g., ADHERENS.
3) Very narrow intercellular space = 3nm:
e. g., GAP junctions
what the types of cell junctions
Macula Adherens (Desmosome or Spot
Desmosome).
2) Zonula Adherens (Belt Desmosome).
3) Zonula Occludens (Tight Junction).
4) Gap Junction (Nexus).
describe the structure of macula adherens
Location: Between epithelial cells, on lateral cell interfaces with their long axes perpendicular to basement membrane of epithelium.
Shape: Small discoid structures.
Intercellular gap: 25 nm
Adhesive glycoprotein: Desmocollin
Intra-cytoplasmic densities: Attachment plaques beneath plasma membranes of adjacent cells.
Intermediate filaments: Are inserted into attachment plaque or make hairpin loops & turn back into cytoplasm.
describe the function and structure of Hemi-desmosomes
Location: between certain epithelial cells & basal lamina.
Shape: like half a desmosome on epithelial plasma membrane only. Sometimes basal lamina facing the hemi-desmosome is thickened.
Function: To bind the epithelial cells to basal lamina.
describe the structure and location of zonula adherens
Arrangement: as a girdle / belt around each cell that is joined.
Intercellular gap: Normal width (20 nm).
Bridging of gap: No bridge of filaments, though filaments & submembrane cytoplasmic densities are present.
Location: among epithelial cells, fibroblasts & smooth muscle cells.
describe the structure, function and location of zonula occludens
Arrangement: like a girdle.
Intercellular gap: No gap due to apparent fusion of plasma membranes of adjacent cells.
Location: intestinal mucosa & urinary bladder mucosa.
Function: important sealing effect (prevent the change in chemical composition of urine).
describe the structure, function of gap junctions
Intercellular gap: 2-3 nm only. It is traversed by hollow tube-like structures.
Function: permeable to colloidal substances without entering the ECF . Provide communication channels between adjacent cells. Also role in spread of electric impulse from one cell (smooth / cardiac cell) to another.
Desmosomes Vs Nexus:
Nexus usually form limited attachment plaques like
desmosomes, but sometimes more extensive.
Connexons: hexagonal arrays of protein units. Six subunits surrounding a channel.
Regulators of diameter of channels:
Increase in Ca2+ concentration causes the subunits to slide together, reducing the diameter of the channel.
Diameter may also be regulated by pH and voltage
describe the structure of gap junction
Each connexon is made up of six subunits.
Each connexon in the membrane of one cell lines up with a connexon in the membrane of the neighboring cell
forming a channel through which substances can pass from one cell to another without entering the ECF
where are gap junctions located
Cardiac & smooth muscles,
Liver, kidney, thyroid, pancreas, adrenals,
Urinary bladder,
Nervous system (between neurons & between glial cells),
Skin.
what is junctional complex
describe its structure and location
Series of cell junctions between adjacent epithelial cells = junctional complex.
Location: small
intestinal mucosa.
Comprises of:
Zonula occludens + zonula adherens + macula adherens.
what are the functions of glycocalyx
Negative charge of glycocalyx repels other negative charges.
Glycocalyx of some cells attaches to glycocalyx of other cells, thus attaching them together.
Many CHO act as receptors for binding hormones. This attachment with hormones activates attached internal proteins thus activating a cascade of intracellular enzymes.
Some carbohydrates enter into immune reactions.
Repels other negative charged objects
Attaches Glycocalyx of other cells
Act as receptor substances for binding hormones such as Insulin
Involved in some immune reactions (Infections)
Defense against cancer
Embryonic development
Fertilization
describe myelinogenesis
Formation of myelin sheath around the axon.
In peripheral nerve, it starts at 4th I.U month.
It is completed in 2nd year after birth.
Myelin sheath is produced by layers of Schwann cells.
Outermost layer of Schwann cells remain as neurilemma / Sheath of Schwann.
Cytoplasm of Schwann cells is not deposited.
what is the general classification of nerves in guyton
use book bitch
during nerve degeneration changes take place at which levels
) nerve cell body / soma.
2) central stump (nerve fiber central to the site
of lesion) / retrograde degeneration.
3) changes in distal stump (wallarian degeneration).
describe changes in nerve soma during degeneration
Nerve cell body swells
chromatolysis (dissolution of Nissl granules)
nucleus pushed aside
Mitochondria, golgi apparatus, ribosomes & lysosomes 🡪 structural changes.
If axon is cut quite close to cell body 🡪 cell may die.
describe changes taking place in central stump during degeneration
Degenerated area usually extends upwards up to 1 or 2 nodes or more.
Degeneration 🡪 repair soon follows.
describe changes that take place in distal stump during nerve degeneration
Axon & myelin sheath completely degenerate (secondary / Wallerian degeneration).
Simultaneous degeneration throughout length of nerve fiber.
Changes appear in 24 hrs & complete in 3 wks.
Continued conduction for 3 days post injury.
After 5th day all function is stopped.
what are the histological changes that take place during nerve degenerations
Axoplasm 🡪 breaks up into short segments.
Swelling of neurofibrils 🡪 become tortuous & disappear after sometime.
Within few days, space containing axoplasm shows only a little debris.
Myelin sheath disintegrates 🡪 fat droplets appear (8th to 32nd day).
Lecithin molecules present in myelin sheath 🡪 completely hydrolyzed to glycerol, fatty acids, phosphoric acid & choline 🡪 removed by increased number of macrophages (appearing as foam cells due to their high lipid content) or by blood stream.
Endoneurium remains intact within endoneurial tubes.
Schwann cells proliferate & their increased number along with fibrous tissue 🡪 false neuroma. (True neuroma in regeneration)
discuss stages of nerve regeneration
If slight axon injury or injury away from cell body 🡪 nerve cell body shows signs of repair. Nissl granules reappear. Nucleus resumes central position. Nucleolus moves to periphery of nucleus. Full recovery may take 3-6 months.
At the onset of repair 🡪 axon in the central end of cut fiber elongates 🡪 large number of fibrils (up to 50) 🡪 enter the periphery of endoneurial tubes 🡪 only 1 fibril survives 🡪 tubes with fibrils are slowly surrounded by myelin sheath by activity of Schwann cells.
discuss mechanism of regeneration
Less understood.
Factors believed to be responsible:
Neurotrophic stimuli (? Chemical in nature)
what are neurtrophins and their functions
A number of proteins necessary for survival and growth of neurons
Some are isolated from muscles / other structures innervated by neurons
Others are produced by astrocytes
These proteins bind to receptors at neuron endings 🡪 internalized 🡪 transported by retrograde transport 🡪 neuronal cell body 🡪 produce proteins for 🡪 neuronal development, growth & survival.
Other neurotrophins: produced in neurons 🡪 transported in anterograde fashion 🡪 nerve ending 🡪 maintain the integrity of postsynaptic neuron.
what are the different neurotrophins and their receptors
Nerve growth factor
(NGF)
trk A
Brain-derived neurotrophic factor (BDNF)
trk B
Neurotrophin 3 (NT-3) trk C, less on trk A and trk B
Neurotrophin 4/5 (NT-4/5)
trk B
describe prognosis of nerve degeneration and regeneration
If nerve was cut but 2 ends were close to each other 🡪 good result.
If crushing injury 🡪 excellent fuctional results of regeneration.
If gap between central & peripheral ends is more than 3mm 🡪 fiber intermesh & form tumor like swelling (true neuroma) 🡪 very painful in case of sensory nerves.
True neuroma: neuroma that arises from the distal end of the central stump (frequent complication of amputations).
what is true neuroma
Formed during regeneration
During regeneration, if the gap between the central and peripheral ends of the fiber is more than 3mm, the fibers tend to intermesh and form a tumor like swelling called neuroma. It rises from the distal end of the central stump and is called ‘true neuroma’.
It is very painful if present in sensory nerves
what is false neuroma
Formed during degeneration
Schwann cells proliferate and increased number along with fibrous tissue give rise to production of false neuroma
Not painful.
where and why does no regeration take place
Optic nerve fibers & in CNS.
Sprouting of axons 🡪 regeneration fails to occur due to:
1) lack of endoneurial tubes in CNS 🡪 regenerating axons cannot be guided.
2) oligodendrogliocytes (counterparts of Schwann cells in CNS) fail to serve as Schwann cell do.
3) astrocyte activity 🡪 gliosis (formation of scar tissue)
describe function and characteristics of nerve grafts
Nerve graft can be used to join 2 ends of cut nerve trunk if not possible to suture them surgically.
Graft is obtained from patient himself.
Satisfactory results in many cases.
In spite of anatomical regeneration in a mixed nerve trunk, functional disturbances may appear because many nerve fibers may make functional connections with different nerve endings.
If a motor nerve fiber makes connection with a sensory nerve fiber, the area supplied by this sensory fiber will lose sensations.
what is the effect of cutting a mixed nerve trunk (motor, including autonomic & sensory fibers):
S = Sensation loss M = Motor activity loss A = Autonomic nerve activity loss R = Reflex action loss T = Trophic action loss
what are properties of skeletal muscle fiber
Excitability Contractility Tetanization Conductivity All or none law Refractory period Summation Fatigue
what are the properties of nerve fiber axon
Excitability (Strength Duration curve). Electrical potentials (spike potential) Tetany. Myelin sheath. Diameter & Conductivity. All or none law. Refractory period. Summation (Temporal & spatial) Non fatigue-ability
what are properties of action potential
Sudden / abrupt in onset.
Of limited magnitude / amplitude.
It goes to +35 to 40 mV & comes back. (biphasic)
Short duration (may be few millisec).
It obeys all or none law. (if a stimulus is threshold or suprathreshold 🡪 action potential is produced with its maximum amplitude, if subthreshold stimulus 🡪not produced at all).
Self propagating. (automatically propagated in both directions).
Has a refractory period. (when there wont be response to 2nd potential).
describe the parts of refractory period
Absolute: During depolarization & first 1/3 of repolarization. Here sodium inactivation gates are still closed & will not open till potential reaches resting value.
Relative: From end of first 1/3 of repolarization to the beginning of after depolarization (here stronger stimulus can produce action potential).
Super normal period: During After depolarization, there is super normal period. Tissue is most excitable. Here potential is – 65 mV, so small change is required to stimulate.
Sub-normal period: During After hyper-polarization it occurs, because tissue is difficult to be excited because potential becomes – 95 mV.
what is rheobase
it is the voltage/strength of stimulus, required just to excite the tissue ,e.g, 1mV.
what is utilization time
The time for which Rheobase must be applied, to excite the tissue is utilization time ,e.g, 2 ms.
what are chronaxie
Chronaxie: A time for which a stimulus double the rheobase (i-e., 2 mV) when applied, just excites the tissue ,e.g., 1 ms.
what is summation
Adding up of effects of stimuli particularly if stimuli are subthreshold.
On a single motor neuron, thousands of synaptic knobs terminate to
form synapses.
About 80% of these synapses are on dendrites, remaining on cell
body & few on axons.
So single impulse coming to motor neuron through a synapse, cant excite a motor neuron & there must be summation of effects of stimuli.
what is temporal summation
Impulses transmit through 1 or few synaptic knobs repeatedly 🡪 effects on post-synaptic neurons are added 🡪 stimulation.
Second stimulus must fall when effect of 1st one is still there.
what is spatial summation
Impulses are conducted along a number of synapses simultaneously 🡪 effects on postsynaptic neuron are added 🡪 excitation.
what is tetany and its cause
Hyperexcitability of nerve
Common Cause: hypocalcemia,
Parathyroid deficiency,
what is tetanization and its cause
Hyperexcitability of skeletal muscle
Common cause: Claustridium Tetani bacteria.
what is the mechanism of tetany
what is the mechanism of tetanization
what are action potentials
Action potentials are rapidly developing
electrochemical changes occurring in the cell membranes of excitable cells
how are action potentials produced
subthreshold timulus produces no AP
local change in membrane potential
no propagation
suprathreshold stimulus generates AP which propagates
what are the properties of action potentials
upto 100 m/s speed
avg speed 10-20 m/s
0.1 sec delay between muscle nd sensory neuron action potential
what are the phases involved in action potential
resting latent period depolarization repolarization hyperpolarization
what are the channels involved in action potential
voltage gated sodium and pottasium
Na-K pump
describe resting action potential
Na and K channels are closed
Na activation gates closed
inactivation gates are open
describe depolarization in action potential
if suprathreshold stimulus is observed
activation gate opens (quickly)
inactivation gates slowly close
K channel gates slowly open
describe repolarization phase of action potential
Na channel gates close
K channel gate open
pottasium leaves cell
describe hyperpolarization in action potential
potassium gates slowly close resulting more potassium leaving than required resting in hyperpolarization
Na-K pump corrects the ion concentration another impulse can take place
what is absolute refractory period
as long as Na inactivation gates are open
no stimulus will take place
what is relative refractory period
as long as K gates are open
only strong stimulus can open Na gates
what is myosin
Component of thick filament
Protein molecule consisting of two identical subunits shaped somewhat like a golf club
Tail ends are intertwined around each other
Globular heads project out at one end
Tails oriented toward center of filament and globular heads protrude outward at regular
intervals
Heads form cross bridges between thick and thin filaments
Cross bridge has two important sites critical to contractile process
An actin-binding site
A myosin ATPase (ATP-splitting) site
what is actin
Primary structural component of thin filaments
Spherical in shape
Thin filament also has two other proteins
Tropomyosin and troponin
Each actin molecule has special binding site for attachment with myosin cross bridge
Binding results in contraction of muscle fiber
what is the function of troponin in muscle contraction
When not bound to Ca2+, troponin stabilizes tropomyosin in blocking
position over actin’s cross-bridge binding sites
When Ca2+ binds to troponin, tropomyosin moves away from blocking
position
With tropomyosin out of way, actin and myosin bind, interact at
cross-bridges
Muscle contraction results
what is the function of troponin in muscle contraction
When not bound to Ca2+, troponin stabilizes tropomyosin in blocking
position over actin’s cross-bridge binding sites
When Ca2+ binds to troponin, tropomyosin moves away from blocking
position
With tropomyosin out of way, actin and myosin bind, interact at
cross-bridges
Muscle contraction results
what are the steps in contraction of muscle
An action potential travels along a motor nerve to its endings on muscle fibers.
At each ending, the nerve secretes a small amount of the neurotransmitter
substance acetylcholine.
The acetylcholine acts on a local area of the muscle fiber membrane to open
multiple “acetylcholine’’ gated channels through protein molecules floating in
the membrane
Opening of the acetylcholine-gated channels allows large quantities of sodium
ions to diffuse to the interior of the muscle fiber membrane. This initiates an
action potential at the membrane.
The action potential travels along the muscle fiber membrane in the same way
that action potentials travel along nerve fiber membranes.
The action potential depolarizes the muscle membrane.
Here it causes the sarcoplasmic reticulum to release large quantities of calcium
ions that have been stored within this reticulum.
Calcium combines with troponin C. It causes tropomyosin to uncover the active
sites of actin
Cross bridge of myosin interacts with it
Actin myosin sliding and contraction
what are the steps in relaxation of muscle fiber
After a fraction of a second, the calcium ions are pumped back into the
sarcoplasmic reticulum by a Ca++ membrane pump, and they remain stored in
the reticulum until a new muscle action potential comes along;
This removal of calcium ions from the myofibrils causes the muscle contraction
to cease.
Cessation of actin myosin interaction
what is the sliding filament mechanism of muscle contraction
In the relaxed state, the ends of the actin filaments extending from two successive Z
discs barely overlap one another.
Conversely, in the contracted state, these actin filaments have been pulled inward
among the myosin filaments
Also, the Z discs have been pulled by the actin filaments up to the ends of the myosin
filaments. Thus, muscle contraction occurs by a sliding filament mechanism.
This inward sliding is caused by forces generated by cross-bridges with actin
filaments.
It activates when action potential arrives, Ca release from sarcoplasmic reticulum
causes activation of forces b/w actin & myosin leading to contraction
describe in the walk-along theory in detail
Before contraction begins, the heads of the crossbridges bind with ATP.
The ATPase activity of the myosin head immediately cleaves the ATP
but leaves the cleavage products, ADP plus phosphate ion, bound to the
head.
In this state, the conformation of the head is such that it extends
perpendicularly toward the actin filament but is not yet attached to the
actin.
When the troponin-tropomyosin complex binds with calcium ions, active sites
on the actin filament are uncovered, and the myosin heads then bind with these.
The bond between the head of the cross-bridge and the active site of the actin
filament causes a conformational change in the head, prompting the head to tilt
toward the arm of the cross-bridge. This causes Power Stroke
Once the head of the cross-bridge tilts, this allows release of the ADP and
phosphate ion that were previously attached to the head. At the site of release of
the ADP, a new molecule of ATP binds. This binding of new ATP causes
detachment of the head from the actin.
After the head has detached from the actin, the new molecule of ATP is cleaved
to begin the next cycle, leading to a new power stroke. That is, the energy again
“cocks” the head back to its perpendicular condition, ready to begin the new
power stroke cycle.
When the cocked head (with its stored energy derived from the cleaved ATP)
binds with a new active site on the actin filament, it becomes uncocked and once
again provides a new power stroke.
The movement of myosin on actin is called Walk Along Theory or Ratchet
theory
what is isometric contraction
when the muscle does not shorten during contraction
no work is done
joint angle muscle length does not change
only 3-5% muscle shortening
tendons are stretched
what is isotonic contraction
when the muscle shorten but tension on the muscle remains constant throughout the contraction against constant load
work is done
muscle shortens ore than 3-5% to neutralize stretching the elastic component
used to compare functional characteristics of different muscles like fast and slow fibers
what is summation
adding together of individual twitch contractions to increase the intensity of overall muscle contractions
what are the two ways by which summation occurs
by increasing number of motor units contracting simultaneously (multiple fiber summation)
by increasing the frequency of contraction (frequency summation) and can lead to tetanization
what is multiple fiber summation
when CNS sends weak signal to muscle fibers initially less motor units are recruited as the strength of the signals increases more and more motor units begin to respond as well and magnitude of muscle contraction increases. this is called size principle
what is tetanization
muscle is stimuated it contracts
frequncy of stimulation increases
new contraction occurs before the preceding one
second contration is partially added to the first
stregth of contraction increases progressively with increasing frequency
frequncy reached a critical level
successive contraction become so rapid they fuse
whole muscle contraction apears to be smooth and continuous
frequency increaes slightly
stregth of contraction reaches max
any increase in frequncy will result in no effect
this occurs becasue calciummm ions are maintained in muscle sarcoplasm between action potentials
what is excitation coupling
process by which depolarization of muscle fiber initiates contraction
the action potential from NMJ travels along sarolemma into T-tubules
which stimulates DHPR receptors on terminal cisterns which open ryanodine channels allowing calcium efflux into sarcoplasm
define triad
1 T-tubule and 2 cistern on SR
what is calsequestrin
protein present in SR attached to calcium
what is DHPR
dihydropyridine receptor
what is NMJ
A neuromuscular junction is an area of contact between a muscle fibre and a neuron.
what is NMJ composed of
A neuromuscular junction thus consists of:
Presynaptic terminal (Nerve fibre) with vesicles containing the NT
A synaptic cleft (20-30 nm wide)
A synaptic trough or gutter (Muscle fibre) which has numerous folds called subneural clefts.
Neuroreceptors for the NT.
describe the process of exocytosis of Ach
The presynaptic membrane of the neuron contains linear dense bars. To each side of the dense bars are protein particles penetrating the neural membrane. These are the voltage-gated calcium channels.
When an action potential spreads over the terminal, these channels open and allow calcium ions to diffuse from the synaptic space to the interior of the nerve terminal.
The vesicles then fuse with the neural membrane and empty their acetylcholine into the synaptic space by the process of exocytosis.
what are the properties of Ach receptors
Each Ach receptor complex has a total molecular weight of 275,000.
Each receptor complex is composed of 5 subunits:
- 2 alpha
- 1 beta
- 1 gamma
- 1 delta.
The channels remains closed unless 2 Ach molecules attach to the 2 alpha subunits which open the gate.
The opened acetylcholine channel has a diameter of about 0.65 nanometer, which is large enough to allow the important positive ions— Na+, K+ and Ca++ —to move easily through the opening.
what are the steps involved in generation of end plate potential
An AP reaches the presynaptic terminal of the NMJ.
The change in voltage causes the opening of the voltage-gated calcium channels which cause exocytosis of the Ach containing secretory vesicles.
The NT Ach is secreted into the synaptic cleft.
Ach crosses the synaptic cleft to reach the subneural clefts which contains the Ligand-gated Ach channel.
The channels are activated and open allowing the Na+ to move to the inside of the muscle fiber. As long as the Ach is present in the synaptic cleft, it keeps activating the Ach channels which remain open.
The influx of Na+ into the muscle lead to the initiation of the END PLATE POTENTIAL (EPP).
what is end plate potential
At the motor end-plate, the large influx of the Sodium ions leads to a large number of positive charges pouring into the muscle.
This creates a local positive potential change inside the muscle fiber membrane, called the end plate potential. It is usually about 50-75 mv.
In turn, this end plate potential initiates an action potential that spreads along the muscle membrane and thus causes muscle contraction.
describe degradation of Ach
The Ach present in the synaptic cleft is broken down by the enzyme Acetylcholinesterase, into Acetyl coA+ choline.
Both the products are reuptaken by the presynaptic terminal.
The Ach is again synthesized by the nerve cell body and then send by anterograde flow to the presynaptic terminal for packaging into secretory vesicles.
describe the safety factor at NMJ
end plate potential as that required to stimulate the muscle fiber. Therefore, the normal neuromuscular junction is said to have a high safety factor.
However, stimulation of the nerve fiber at rates greater than 100 times per second for several minutes often diminishes the number of acetylcholine vesicles so much that impulses fail to pass into the muscle fiber. This is called fatigue of the neuromuscular junction, and it is the same effect that causes fatigue of synapses in the central nervous system when the synapses are overexcited.
Under normal functioning conditions, measurable fatigue of the neuromuscular junction occurs rarely, and even then only at the most exhausting levels of muscle activity
describe propagation of action potentials
Local circuit of current develop
Depolarization spreads along entire length of fiber
Nerve/ muscle impulse
what is all or none principle
Once an action potential is generated, it travels along entire length of fiber if conditions are favorable
Or doesn’t travel at all if conditions aren’t favorable
what is synaptic transmission
Nerve impulse comes from nerve terminal 🡪
depolarization of membrane of synaptic knob 🡪 voltage
gated Ca++ channels open up in the membrane 🡪 Ca++ ions
move into synaptic knob 🡪 agitation of synaptic vesicles
🡪 vesicles fuse with membrane of synaptic knob 🡪
release of neuro-transmitter by exocytosis.
describe EPSP
Resembles EPP (end plate potential). There is localized hypo-polarization due to Na+ influx.
Resting potential of cell body of neuron is
-65mV.
Example of Excitatory neurotransmitter is adrenaline and acetylcholine.
When EPSP is produced 🡪 hypo-polarization 🡪 potential becomes less negative 🡪 reach threshold of excitation (-45mV) 🡪 ACTION POTENTIAL in cell body.
what is the purpose of EPSP
To bring potential of membrane to threshold
(-45mV)
It is graded like EPP (directly proportional to amount of neuro-transmitter released).
There is no refractory period.
Not self propagating like EPP.
describe IPSP
Produced when post-synaptic neuron is
inhibited.
Neuro-transmitter is of inhibitory type (GABA. Glycine)
It binds with receptors on post-synaptic
membrane 🡪 change in permeability of
membrane for K+ or Cl- (there is opening of
K+ or Cl- channels 🡪 efflux of K+ 🡪 cell
becomes more negative 🡪 hyper-polarization / IPSP.
Opening of Cl- channels 🡪 extra-cellular Cl- moves
into the cell 🡪 more negative 🡪 hyper-polarization /
IPSP.
what is the effect of IPSP
Because of IPSP, resting potential which is
-65mV, becomes -70 to -75mV 🡪 Post-synaptic neuron is inhibited 🡪 POST-SYNAPTIC INHIBITION.
PRE-STNAPTIC INHIBITION:
Synaptic knob has additional synapse with other nerve terminals 🡪 release of inhibitory neuro-transmitter from additional synapse🡪 synaptic knob is inhibited 🡪 no further transmission from synapse now to post-synaptic neuron
difference between EPSP and AP
Magnitude
Low
High
Propagation & Duration
Nil; it remains localized ( up to 20 msec)
Self propagating ( up to 2 msec)
Refractory period
absent
present
All or none law
Not obeyed. It is graded.
obeyed
Decrement (decline of size with distance)
present
Absent. Size is constant
Increased permeability to ions
To Na+ & K+ at one time but Na+ influx > K+ efflux
Na+ first, then K+
describe properties of EPP
It is a local potential of motor end plate, i-e., the thickened muscle membrane that is supplied by a motor-neuron, thus forming a component of neuro-muscular junction.
Local potential recorded only at End plate region.
It varies with strength of stimulus / amount of neurotransmitter released. It can show summation.
In Myasthenia Gravis, Miniature End Plate Potentials (MEPP = 0.5 mV) are produced. It is a rare auto-immune disease.
Because of EPP 🡪 Threshold for action potential is reached (-65 mV).
If RMP is -90 mV, then threshold is -65 mV, we need 25 mV potential change.
Purpose of EPP is to reach the threshold of action potential.
So voltage of EPP is much more than required, because required is only 25 mV.
It is called SAFETY FACTOR.
what is Dales law
At a given synapse, only 1 type of neurotransmitter is released, it may be excitatory or inhibitory.
Later on it was found that in certain cases 🡪 release of additional substances at a given synapse
e.g., in noradrenergic synapses: along with nor-epinephrine, some dopamine, octopamine, dopamine-beta hydroxylase, neuropeptide Y & prostaglandins are also released, although their role is ?? (not fully known)
what is law of forward conduction
Through synapses, impulses are conducted always from pre-synaptic to post synaptic neuron, never in backward direction.
(NO REVERSE GEAR!!)
what is synaptic delay
SYNAPTIC DELAY:
At a synapse, there is delay due to time taken in events during synaptic transmission. Through each synapse, there is delay of 0.5 milli seconds.
describe fatique of synaptic transmission
If impulses are conducted through a synapse repeatedly 🡪 fatigue due to exhaustion of stores or progressive inactivation of receptors on post-synaptic membrane.
Fatigue of synaptic transmission is protective in nature 🡪 termination of epileptic fit.
describe summation in synapses
Adding up of effects of stimuli particularly if stimuli are subthreshold.
On a single motor neuron, thousands of synaptic knobs terminate to form synapses.
About 80% of these synapses are on dendrites, remaining on cell body & few on axons.
So single impulse coming to motor neuron through a synapse, cant excite a motor neuron &
there must be summation of effects of stimuli.
describe temporal summation in synapses
Impulses transmit through
1 or few synaptic knobs repeatedly 🡪 effects on post-synaptic neurons are added 🡪 stimulation.
Second stimulus must fall when effect of 1st one is still there.
spacial summation in synapses
Impulses are conducted along a number of synapses simultaneously 🡪 effects on postsynaptic neuron are added 🡪 excitation
describe tetanic facilitation or potentiation
If impulses are conducted through a synapse rapidly 🡪 then rest is given to synapse 🡪 then again impulses are conducted 🡪 response of post-synaptic neuron is increased.
Calcium ions enter in synaptic knob in each transmission, before fatigue occurs 🡪 increase no. of calcium accumulate in knob 🡪 more neurotransmitter released 🡪 more EPSP.
After fatigue 🡪 if rest is given 🡪 more calcium ions become available 🡪 facilitation.
describe excitability and depresses in synaptic transmission
ALKALOSIS INCREASE EXCITABILITY OF SYNAPSES,
ACIDOSIS DEPRESSES SYNAPTIC TRANSMISSION:
Increase excitability Caffeine (cerebral stimulant) Theophylline Strychnine / Kuchla (opisthotonus) Decreased calcium (tetany)
Decrease excitability
Anesthetics
Hypoxia
Increased calcium (stabilize)
