Physiology-Endterm Flashcards
Function of cellular junctions
- Mechanical stability
- Sepration of membrane domains
- Signal conduction between cells
- Maintaining integrity during contraction
- Binding growth factors together (ex: neurons growth core guidance)
- Help in cell migration, wound healing, phagocytosis
Tight junction (occluding junctions)
Separates 2 things in epithelial cells
- Different compartments of fluids from each other
- Apical and basolateral surface
Tight junctions are located below the apical surface
Makes sure nothing unregulated enters or exits the cell
Tight junction proteins
Claudius and occludens
Each claudin connects to another claudin and the same for occludens
Claudin
Major part of the tight junctions
Occludens
Don’t know the function of it
Tight junctions and role in glucose transport
Need to bring glucose from the lumen to the blood. So have glucose transporters that are secondary active transporters that bring glucose from the lumen to the cell. Have glucose carriers that work by facilitated diffusion to bring glucose to the blood. Have high glucose in cell and low in lumen.
Tight junctions make sure that the glucose transporters and the glucose carriers stay in their respective side
Heregulin
Secreted by epithelial cells. Helps stimulate cell repair during injury. Heregulin is located in the apical surface while while it’s receptors are located in the basolateral surface.
Tight junctions and heregulin
Tight junctions make sure that heregulin and its receptors stay on their respective side during normal times.
When the cell is injured, tight junctions will disappear allowing heregulin to bind to its receptor and heal the cell. This is an autocrine process
Desmosomes
Maintains the integrity of the cell. Found in places that are exposed to mechanical stress. Is an adhering junction.
Has an attachment plaque
Attachment plaque
Make of desmoplakin, plakoglobins, and plakophikin. Plakophikin connected desmoplakin and plakoglobins together.
The attachment plaque is connected to keratin which then connects it to the cytoskeleton
Extracellular side of desmosomes
Connected by adhering proteins such as cadherins to connect attachment plaques to each other
If no desmosomes…
Cells are transformed to metastatic cancer cells that can move around freely
Anchoring junction
Anchor between
- Other cells
- Basolateral surface to the basal lamina
Has intracellular attachment proteins and transmembrane adhesion proteins
Transmembrane adhesion proteins
The proteins that connect to the surfaces
Intracellular attachment proteins
Binds to the transmembrane adhesion proteins
Gap junctions
Channels that allow ions and small molecules to pass through. Made of connexons
Connexons
Hexagonal tubes that are make of 6 connexins
Advantages of gap junctions
Are really fast
A lot of insects have them as their main signaling mechanism which is why there are so fast
Disadvantages of gap junctions
The signal is bidirectional
Function of gap junctions
- Allows cells to work all together since if one cell is depolarized, the next cell will be as well (In smooth and cardiac muscle)
- Helps in signal transduction pathways
Integrins
Connects the cytoskeleton to the ECM by ECM proteins and the adaptor protein
Helps in cells migration, wound healing, and macrophages
Adaptor proteins
Interacts with keratin and actin filaments of the cytoskeleton
ECM proteins
Collagen, laminin, and fibronectin
Mechanism of Integrins
- Integrins are in the inactive or bent form
- Signal transduction pathway will phosporlate talon and talon will activate Integrins by getting rid of the mask on the ECM binding side and dimerizing the integrins together
- Ingegrins bind to the specific ECM protein
- Focal-adhesion molecules will recruit intracellular proteins to hold the integrin in place (vincillin and actin)
Cytoskeleton
Made of actin and myosin
Actin
Small protein that has 2 forms
- G-actin: monomer
- F-actin: polymer
Can work by itself or with myosin
Myosin II
Most abundant type and found in muscle cells
Myosin I and V
Found in non-muscle cells
Microfilaments
Made of F-actin and bound proteins
Thinnest filaments of the cytoskeleton
Polymerization of actin (nucleation)
G monomer has clefts to which ATP binds. Mg is needed as a cofactor (ATP binds here). Binding of ATP leads the G monomer to be converted to F-actin which is a double helical form
Equilibrium between…
G actin and F actin forms
Part of actin
Has 2 parts:
- Positive end
- Negative end
Positive end
Activated G actin can easily be attached and elongate the actin filaments
Negative end
Depolymerization happens here and stabilizes the structure
Cytochalasins
Inhibit polymerization and activate depolymerization
Bad since the cell doesn’t have any support so is weak
Phalloidans
Inhibit depolymerization and activates polymerization
Bad since the cell doesn’t need that much actin
Actin location
Located at the peripheral regions of the cell since this is where the cell moves
Actin function
- Stabilize periphery of cell
- Responsible for cell shape
- Allows cell movement
- Can generate force with myosin
Cell movement by actin
- Integrin-shuttle movement: cell rolls on its membrane due to actin and integrin is inserted through the front of the cell
- Transcytosis: actin helps move the materials through the cell
- Elongation of membrane: actin helps vesicles fuse into the membrane to elongate it
Myosin I
Small motor protein that works with actin
Has 2 domains:
- TH1 domain
- Motor domain
Motor domain
Binds to actin
Has nucleotide binding pockets where ATP and ADP bind
TH1 domain
Binds to the vesicle/organlelle
Neck region
In between the two domains
Myosin I function
- Membrane cytoskeleton adhesion: provides integrity to the cell
- Endocytosis/exocytosis: in endocytosis, myosin pulls the material inwards
- Vesicle shedding: myosin helps move cell membrane parts out of the cell (ex: mammary glands)
- Channel gating/adaptation: helps in signal transduction (ex: hair cells)
Myosin V
Helps transport organelles and vesicles
Myosin V mechanism
ADP is bound the to the two motor domains so it’s in the waiting state. When an ATP replaces the ADP, the motor domain moves and takes a step forward and lands in the 13th actin unit. This process is repeated until finally, ATP is hydrolyzed and myosin V goes back to the waiting state
Microtubules
Made of alpha and beta tubulin.
Alpha and beta tubulin form a row called a protofilament with the help of GTP
13 protofilaments together will form a tubulin structure and this structure is tubular
Parts of microtubules
Have two ends
- Positive end: beta tubulin on this side and GTP tubulin is added so elongation on this side
- Negative end: alpha tubulin and GDP tubulin is here so it falls apart. Need a GTP molecule to be added here in order to keep the molecule together. This is known as catastrophe and rescue
Function of microtubules
- Transport (this is really fast and done by microtubules since actin and myosin are too slow)
- Helps in mitosis (organized in centrosomes)
- Helps in cell shape
Microtubules associated proteins (MAPs)
Can be divided into:
- Non-motor proteins
- Motor proteins
Nonmotor proteins
Helps organize the microtubules
Have MAPI(MAPS1 and MAPS1B) and MAPS II (MAPS2 and MAPS 4 and tau)
MAPSII
Attach vesicles to the ER
Motor MAPS
Have kinesin and dyenin
Have a similar walking mechanism to myosin V and walk in opposite directions
Dyenin
Retrograde transport so goes from cell membrane to ER
Kinesin
Is anterograde transport so goes from ER to cell membrane
Cilia
Microtubules that help remove cilia in the respiratory tract. Turns like a propeller to expel material
Organized into 9+2 and have A and B tubules and connected by dyenin
Dyenin helps the cilia move very slowly in a clockwise manner
Flagellum
A long cilia that has one turning to move and the other turning in the opposite direction to move things out of the way
Intermediate microfilaments
Very string microfilaments and part of the cytoskeleton
Provide mechanical support and shape maintenance
Help connect desmosomes together
Structure of intermediate microfilaments
IFs are intertwined into a dimer to form a double helix.
2 dimers come together to form a tetramer
8 tetramers make an IF
Myosin
Anisotropic so doesn’t allow light pass through and this is why the A band is dark
Main component of thick filaments
Has three parts:
- Head: attaches to actin
- Neck
- Tail
H zone
No intersection between actin and myosin so that’s why it’s light
Thin filaments
Have actin, troponin, and tropomyosin
Held in place by the Z disc
Thick filaments
Held in place by the M line
Actin
Is isotopic so allows light to pass through
F-actin provides the backbone of the thick myofilament
Tropomyosin
Is in the grooves of the F actin
Helps expose the actin when it’s time for contraction
Troponin
Attaches to tropomyosin and made of:
- Troponin C: high affinity for calcium
- Troponin I: high affinity for actin
- Troponin T: high affinity to tropomyosin
Contraction
In the waiting state, ATP is bound to the myosin head
When it is hydrolyzed, myosin head begins to prepare to attach to actin
Attaches to actin and forms a cross-bridge
Inorganic phosphate is released and the myosin flocks the actin forwards
Role of calcium
Calcium binds to troponin C which begins the whole process
Muscle excitation
Acetylcholine is the main neurotransmitter and stimulate an action potential which allows T-tubules to allow the sarcoplasmic reticulum to allow calcium to release into the cytoplasm to allow it to bind to troponin C
When contraction is done, calcium goes back to the sarcoplasmic reticulum
Sliding filament theory
The thick and thin filaments don’t change their length during contraction. They just slide over each other
A band length in contraction…
Stays the same
H band length during contraction…
Gets smaller and almost disappears
I band length during contraction…
Become smaller
Twitch
When muscle is stimulated with a single shock, it contracts and relaxes very quickly
Graded summation of twitch
When one shock is given and then another, the shock is added onto the previous one to make the response higher since not all the calcium has gone jack to sarcoplasmic reticulum
Tetanus
Giving a lot of stimulus one after another
Can be incomplete or complete
Incomplete tetanus
There is small resting period in between but stimulation is still frequent
Complete tetanus
Stimulation frequency is highly increased and almost no resting period in between
Ideal muscle length
2-2.5 micrometers
Long fibers
3.65 micrometers. This results in no overlap of actin and myosin so no contraction can take place
Short fibers
1.65 micrometers and fibers are always overlapping so also no contraction
Isotonic contraction
Length of muscle changes but force is constant
Two types
- Concentric
- Eccentric
Concentric
Length of muscle decreases
Ex: muscle lifting
Eccentric
Muscle length increases
Ex: walking downstairs
Isometric
Weight of the muscle doesn’t increase but force used increases since you’re lifting up something that’s really heavy
Ex: lifting up a desk
Motor unit
Motor neuron+all muscles innervated
When stimulus is low, few motor units are recruited and when stimulus is high, higher number of motor units are recruited
Motor units are recruited according to size so first small then large
Cardiac muscle
Are striated and involuntary and have intercalated discs that contain tight junctions and extracellular fluid
Cardiac muscle cells
Are the major cells that contain large amounts of filaments. Generate slow action potential and can’t undergo division or replacement
Pace maker cells
Have small number of filaments and can make their own action potential so depolarizers spontaneously
Once an AP is made, continues for the rest of a lifetime
Found in the SA node
Purkinje cells
Contain in filaments and are impulse conducting cells. Non-differentiated muscle cells that can regenerate
Stimulation of action potential
First sodium enters the cell in the SA node creating a graded potential. Once threshold potential is reached, calcium enters the cell and depolarizers it. Calcium that enters induces calcium in the sarcoplasmic reticulum to be released to induce contraction. When this is done, potassium channels open and calcium goes back to the sarcoplasmic reticulum
Propagation of AP in heart
Begins in the SA node and goes to the internodal pathway and the atrioventricular nodes. From the atrioventricular nodes, goes to atrioventricular bundle (bundle of His), then to atrioventricular branch, and then to purkinje fibers in the apex
If no AP in SA node, still can generate through
- Atrioventricular node
- Atrioventricular bundle
- Purkinje fibers
Contraction force in cardiac muscle
- Intracellular Ca concentration
- Sliding if myofilament
Excitation in cardiac muscle
- Voltage gated Ca channel
- Na/C exchanger on the lateral side
Relaxation in cardiac muscles
- Na/C exchanger on apical surface
- Sarcolemmal Ca-ATPase
- Sarcoreticular Ca-ATPase
Sarcoreticular Ca-ATPase channel
Blocked with phospholambin so need to phosphorylates it in order to activate it
Innervation of the heart
Regulated by the autonomic nervous system
Cardiac centers are in the medulla oblongata
Sympathetic trunk innervates the SA & AV nodes, heart muscles, and coronary arteries
Parasympathetic trunk inhibits SA &AV nodes through the vagus nerve
Smooth muscles
Don’t have striation actin filaments are longer than those in skeletal muscles and myosin is arranged vertically
Contraction of smooth muscle helps regulate blood flow, BP, and compliance
Contraction of smooth muscle
When the cell is depolarized, voltage gated Ca channels open and bind to calmodulin. The complex dephosphorylates myosin light chain kinase and phosphorylates the myosin light chain
To deactivate it, myosin light chain phosphate dephosphorylates myosin light chain. Myosin light chain is activated by dephosphorylation
Degree of contraction in smooth muscles
Is activated myosin light chain kinase is more than myosin light chain phosphates, then it leads to contraction and vice versa
Vasoconstriction
Activating myosin light chain kinase
Requires an elevated amount of Ca in the cytoplasm and get through two ways:
- Bringing calcium from outside to cytoplasm
- Bringing from sarcoplasmic reticulum to cytoplasm
Vasodilation
Activating myosin light chain phosphatase
Bringing calcium inside the cell
- L type Ca channels
- Receptor-operated channels: ligand has to bind to open
- Mechanosensitive channels: responds to touch
- Store-operated channels: used when Ca in sarcoplasmic reticulum is depleted and need more Ca
Bringing calcium from sarcoplasmic reticulum to cytoplasm
- IP3 receptor channels
- Ryanodine channel receptors: open by calcium-induced-calcium release
Regulating L-type channels
- AP from neighboring cells
- Stretching of cells
- Binding if ligand
- Opening Ca-regulated chloride channels
- Inhibiting K channels
By manipulating these receptors, can induce smooth muscle contraction/relaxation
Hyperpolarization/repolarization closes the channels and done by:
- BKa: activates by Ca, NO
- Kv: K voltage channels
- Kir: activates during repolarization
- KATP: inhibited by ATP and open during ischemia
Contraction of smooth muscle with Ca-independent machanism
Angiotensin II binds to its receptor and relaease G12/13. This activated Rho-kinase which phosphorylates myosin light chain phosphatase making it inactive
cAMP and cGMP
Help in relaxation by activating PKA and PKG which help in:
- Inhibiting L-type receptors
- Inhibiting Rho kinase
- Inhibiting IP3
- Activating K receptors
- Getting rid of phospholambin on SERCA receptors
- Inhibits myosin light chain kinase
Phosphdiesterase
Changes cAMP and cGMP and promotes contraction is need to inhibit this
Innervation of smooth muscle
Have neurotransmitter receptors and innervated by autonomic nervous system
Varicosities
Bulge-like shape of neurons that release neurotransmitter
Single unit
Only a couple of smooth muscles are innervated but function as one
Multiple unit
Every smooth muscle is innervated and works independently
Epithelial cells
Organized into sheets and are the intermediates between the lumen of body organs and blood
Function
- Barrier to microorganisms
- Prevent loss of water
- Maintaining homeostasis
Apical membrane
Faces the lumen
Basolateral membrane
Secreted by the cells and faces the blood. Is invaginated to increase surface area to allow Na/K ATPase at the bottom (only place where Na/K ATPase is on top is the choroid plexus)
Claudin
Main proteins that determine the barrier and permeability of tight junctions
Claudin 16
Determine permeability of divalent cations in thick ascending loop of Henle
Claudin 4
Controls permeability to Na
Microvilli
Projections of the cell membrane that help increase surface area. Found in cells that need to transport large number of ions and molecules
Hey microfilaments, actin, and myosin in it but mostly actin
Brush border
On proximal tubule cells and act as sensor and tubular flow
Motile cilia
Help in moving things (e.g. found in respiratory tract to more mucus out of the airways). Arranged in the 9+2 configuration with an axons even connected to a basal part
Nonmotile cilia
Act as mechanoreceptors and sense flow rate and tubular fluid in nephron of kidney
Also establishes left and right as symmetry of organs during embryological development
No motile proteins (actin, myosin). Arranged in a 9+0 configuration
Nephron
Structure of the kidney where urine is formed. Have about a million of the, in one kidney
Blood flow in kidneys
Goes to nephron through afferent arterioles and then hoes to glomerulus and then goes to efferent arterioles into peritubular capillaries
Glomerulus
Place where blood is filtered. Surrounded by Bowmans capsule
Renal vein
Blood collected from the nephron renal vein
Materials traveling through nephron
Proximal tubule then descending thin tubule then ascending thin+thick tubules then distal tubule and then connecting segment (late distal tubule) then collecting duct
Proximal tubule
Has invaginations in the basolateral membrane which increases surface area. Has brush border. Has a lot of mitochondria
Reabsorbed 2/3 of blood
Thin descending+ascending of loop of Henle
Has poorly defined apical and basolateral surfaces. Low mitochondria and few invaginations if basolateral membrane
Thick ascending loop of Henle
Has lots of invaginations in basolateral membrane and a lot of mitochondria
Distal tubule
Have lots of invagination in basolateral surface and lots of mitochondria
Connecting segment & colecting duct
Made of 2 types of cells:
- Principal cells
- Intercalated cells
Principal cells
Are moderately invaginated and work to:
- Reabsorb Na and secrete K
- Help in water movement
Intercalated cells
Plays a role in acid-base balance and is highly invaginated and has a lot of mitochondria
Reabsorption/absorption
Moving from lumen, to apical and basolateral surface to blood
Secretion
Moving from blood to basolateral and then apical surface to lumen
Vectorial transport (paraceloular transport)
Transport along tight junctions of cells. All through facilitated diffusion set up by an electrochemical gradient
K secretion and Na absorption
This is paraceullar transport. Na/K pump (on basolateral side) lumps in K and takes out Na. With high K, K leaves through its leaky channels on the apical side changing the membrane gradient to positive
This allows Na to enter through its channels on the apical surface and in general allows for the absorption of cations
Transcellular transport
Getting through the cell by moving through the apical and then the basolateral and vice versa
One process is active and the other is passive
Uses cotransport and countertransport
Cotransport
Two ions move together in the same direction. Also known as a symporter
Ex: Na-glucose, Na-K-2Cl, Na-3HCO3
Countertransport
Also known as exchangers and antiporters. One molecule moves in and the other molecule moves out
Ex: Na-H exchanger, Na-protein exchanger
Water channels
Also known as aquaporins that help in moving water
They are gated in plant cells so the plant cell doesn’t overflow with water
Aquaporin 1
Located on the apical and basolateral surfaces of the proximal tubule and thin descending loop
No aquaporins on…
Thin and thick ascending tubule
Aquaporins 2
On connecting segment. Located on the apical side and is activated by an anti diuretic to reabsorb water
Also located in cortical collecting duct
Aquaporins 3
Located on outer medullary collecting duct on basolateral surface
Aquaporins 4
Located in basolateral side of inner medullary collecting duct
Uniporters
Bring in only one molecule
Permeability of tight junctions
Regulated by claudins. Proximal tubule and thin descending tube have higher permeability so have loose claudin (claudin 2)
Distal tubule and collecting duct has low permeability so have tight claudins like claiming 3,4, and 8
Regulating epithelial transport by signals
- Retrieve transporters from membrane or insert into the membrane
- Produce new transporters
- Change activity of transporters
Norepeniphrines effect on epithelial transport
Binds to B receptors and stimulates Na and water reabsorption
Aldosterone
Regulated Na levels and helps in secreting K and reabsorbed Na
Blood flow
Movement of blood in vessels
Blood flow (rate)
Total volume of blood that flows through a period of time (L/min)
Velocity
Tells how fast the blood is moving (cm/s)
Cardiac output
Total blood flow out of the heart, has to equal venous return otherwise blood will accumulate in the pulmonary or systemic circulations