patho phys exam 1 Flashcards
CELL-CELL COMMUNICATION
Co-ordination of activity & homeostasis
Achieved by:
– Direct communication:
* Gap junctions - used connexons to connect cells
* Tunneling nanotubes - are thin, long protrusions between cells utilized for intercellular transfer and communication
* Juxtacrine - when two cells are attached to each other
Indirect communication:
* Paracrine
* Autocrine
* Endocrine
* Neuronal
- these occur via chemical messengers
COMMUNICATION VIA GAP JXNS
- Most intimate & rapid means of communication
- allows passage of small molecules and ions
- what connects them: connexons
- cells can communicate with each other very quickly
TNTs are larger and longer in size
Because they are further apart, cells that are further apart can still communicate
JUXTACRINE COMMUNICATION
Direct contact through plasma membranes
- Restricted to cells in contact (cannot diffuse)
- example: Antigen-Antibody reaction, phagocytosis, CAMs (integrins and cadherins), etc.
the proteins on the outside of the cells recognize each other and join together
AUTO/PARACRINE COMMUNICATION
autocrine: secreting cells sends/releases hormone and if the signal goes back and acts on the secretng cell’s receptors then that is autocrine - acting on its own receptor
paracrine: secreting cells send/release paracrine and if the signal binds onto local target cells then that is paracrine
example: histamine, do not reach the blood circulation then it will not be secreted
ENDOCRINE COMMUNICATION
Hormones secreted in blood
- Travel to distant sites
- Acts on cells possessing
receptors; target cells have receptors that can bind to the hormones and only the activity of this cell is effected - FSH, thyroid, insulin, etc.
exocrine: glands that secrete digestive enzymes and they have ducts
endocrine glands are ductless and do not have ducts to carry enzymes to the body so they use the blood to carry the enzymes :)
pathway:
secreting cell (endocrine cell) sends hormones into the blood
- hormones are carried to the distant target cell which have receptors for the hormone
neuronal communication
short-range, released by electrical signals
diffuse to act on target cells (gland/neuron/muscle)
neuron sends neurohormones to the blood and affects distant target cells
neuron sends neurotransmitters and acts on the local target cell (may be a gland, muscle etc)
SIGNAL TRANSDUCTION
Chemical messengers: lipid-soluble or water-soluble
- Signal transduction process: → message (signal) is “transduced” inside the cell by “transducers” (convert one form of energy to another e.g., radio/phone)
- Lipid soluble:
cross membranes → affect gene transcription → affect activity of proteins - Water soluble: do not cross membranes, bind to receptors → transduce signal inside the cell
– 1st Messenger-receptor binding → intracellular events: - By opening/closing ion channels allowing ions to move in/out
- By transferring the signal to the intracellular 2nd messenger
transduce: one form of energy is converted to another form of energy
neurohormones or NTs are the 1st messengers
SIGNAL TRANSDUCTION
I. Pathway used by lipid
lipid soluble:
substances go into cells, bind to receptors, change the activity of genes, affects gene transcription, and change cellular response
ION CHANNELS
leak channels:
- always open
- permit leakage of ions into/out of cells
- electrical conc. gradient
gated channels
- open/close in response to stimuli
- ligand-gated ion channels: chemical messenger binds to a receptor associated with ion channels
- Voltage-gated ion channels: Changes in electrical status of the plasma membrane
Ionic movement leads to the physiological response
SECOND MESSENGER PATHWAYS
types
- tyrosine kinase: the receptors have an enzymatic activity
- GTP-coupled receptors
tyrosine kinase
1 - two extracellular messengers bind to two tyrosine kinase receptor enzymes which pair =, activating receptor-enzyme’s protein kinase (tyrosine kinase) site that faces the cytoplasm
2- tyrosine kinase site self-phosphorylates receptor-enzymes tyrosines
3- inactive designation protein binds phosphorylated rceptor-enzyme which phosphorylates protein activating it
4- active designated protein brings about the desired response
GTP
- cyclic AMP & phospholipase C
GTP
1 - binding of extra-cellular messenger to receptor activates a G protein, the alpha subunit of which shuttles to and activates phospholipase C
2- phospholipase C converts PIP2 to IP3 and DAG
cAMP activates PKA
PLC activates PKC
SECOND MESSENGER PATHWAYS
The message is “relayed” inside the cell via 2nd messenger
- 2nd messengers relay it further to other IC proteins
- Signaling cascade amplifies the initial response
- major ones:
– Cyclic AMP
– Ca2+/DAG - Others exist!
- Disturbances in any part of the processes can lead to diseases
- extracellular chemical messenger bound to a membrane receptor - 1 molecule
- activated adenyl cyclase - 10 molecules
- cyclic AMP - 1000 molecules
- activated protein kinase - 1000 molecules
- phosphorylated (activated) protein (ex: enzyme) - 100,000 molecules
- products of activated enzyme - 10,000, 000
MEMBRANE POTENTIAL
PM is polarized electrically = membrane potential
– Separation of opposite charges across the membrane due to differences in the relative number of cations/anions
- like charges repel and need to be separated and to do that you need energy
- an equal amount of + and - charges on both sides of the membrane. So 10+ outside and inside, 10- outside and inside. There is no membrane potential
- if there are unequal amounts of + and - charges, on both sides of the membrane, now there is membrane potential
- the more charge on either sde, the greater the potential
MEMBRANE POTENTIAL
“Potential” (capacity) to do work
– Unlike charges attract, energy is used to separate them – When allowed to come together, the energy released
– This energy is harnessed to perform work
- The membrane itself is not charged!
- Measured in millivolts (one-thousandth of a volt)
– magnitude of potential Depends on the “degree” of separation
GENERATION OF RMP (resting membrane potential)
The constant membrane potential of tissues at rest: −70mV. The cell is in a resting phase and not activated
- Unequal distribution of Na+, K+ & A- across membrane
– Na-K-ATPase pump - Pumps three Na+ outside and two K+ inside
- Outside becomes more positive than inside, membrane potential!
– Leak channels for Na & K ions - Always open, allow passive diffusion due to concentration gradient
Na+: more in the extracellular space, less in extracellular space
K+: less in the extracellular space, more in the intracellular
A-: less in the extracellular space, more in the intracellular space
K+ tries to move outside of the cell
Na+ tries to move inside of cell
GENERATION OF RMP
Equilibrium potential of K+ (EK+):
- Concentration gradient = electrical gradient
- Given by Nernst equation: not on exam
E = 61 log Co/Ci
EK+ = 61 log 5/150
EK+ = 61 (-1.477)
EK+ = -90mV
K+ will pass through leak channels
conc. gradient tries to push K+ outside
electrical gradient tries to push K+ inside
when these are equal and opposite: this will be the equilibrium potential
GENERATION OF RMP
Equilibrium potential of Na+ (ENa+):
– Concentration gradient for Na+ pushes it in leaving Cl- outside
– Concentration gradient = electrical gradient is the equilibrium potential
– Given by Nernst equation:
E = 61 log Co/Ci
ENa+ = 61 log 150/15
ENa+ = 61 (_______)
ENa+ = _+61____mV
ENa+ lower than EK+: why? - there are MANY MORE K+ leak channels open than Na+ leak channels.
EK+ was -90mV
because it all depends on the conc. gradient
generation of RMP
concurrent effect of Na+ & K+ movement
in a normal cell:
- relatively large net diffusion of K+ outward establishes an EK+ of -90mV
- no diffusion of A- across the membrane
- relatively small net diffusion of Na+ inward neutralizes some of the potential
changes in RMP
polarization: any state, + or - other than 0mV
depolarization: decrease in potential, the membrane is less negative
repolarization: return to resting potential after depolarization
hyperpolarization: increase in potential; membrane more negative
resting potental: -70mV
MEMBRANE POTENTIAL: USE
RMP is -70mV
- Nerve & muscle cells are excitable tissues Undergo transient, rapid changes in their RMP
- Triggering events (like sound waves, or light waves) lead to Membrane permeability changes
then
- Ions move across cell membranes, and then Membrane potential changes
then Electrical signals
types of Electrical signals:
- Graded potentials: Travel short distances
- Action potentials: Travel long distances
functions of electrical signals
- initiate contraction
- Receive, process, initiate & transmit messages
STRUCTURE OF THE NEURON
CELL BODY
- Nucleus & cell organelles
DENDRITES
- Also known as input zone because it is where it receives the message from other neurons
- Increase surface area
- Carry signals toward the cell body
- Contains receptors for neurotransmitters
- Initiate graded potentials which are electrical signals that can generate the action potential
AXON HILLOCK
- Also known as trigger zone (action potentials)
- Abundant voltage-gated sodium channels
AXON/NERVE FIBER
- Single elongated tubular structure
- May be covered in myelin sheath
- Conducts signals away from the cell body
AXON TERMINALS
- Also known as output zone
- Releases neurotransmitters
NEURONAL LINKAGE
By converging input, a single cell is influenced by thousands of others
- postsynaptic neuron
By diverging output, a single cell influences thousands of other cells
- presynaptic neuron
- release neurotransmitters and bind onto the dendrite and cell bodies to generate graded potential
- the graded potential will be summed up as the action potential
- the action potential
go over
GRADED POTENTIALS
- Local changes in RMP that occur in varying grades/strength
- Stimulus leads to an influx of sodium ions: a small depolarization
- A small hyperpolarization is also a graded potential
EXAMPLES
- Receptor potentials
- Postsynaptic potentials
- Pacemaker potentials
- Slow wave potentials
depolarization and hyperpolarization are graded potentials
Can efflux of K+ or influx of Cl- cause GPs?
A
Yes
B
No
A
Yes
K+ leaving the cell
Cl- entering the cell
in both cases, the cell becomes more negative and thus will generate a small hyperpolarization
a small depolarization or hyperpolarization are graded potential
CHARACTERISTICS OF GRADED POTENTIALS
The magnitude & duration of the graded potential is proportional to the magnitude & duration of the triggering event
the magnitude of the graded potential is proportional to the magnitude of the stimulus
increase the duration of graded potential, then increase the triggering event
similar to the hammer-hitting plate game, the harder you hit the higher the metal will go and hit the top
CHARACTERISTICS OF GRADED POTENTIALS
Graded potentials spread by passive current flow in all directions - so energy is not required because it is passive
the potential exists because of the movement of ions, anytime you have ions crossing the membrane you have ion channels
if there is a triggering event or stimulus, the channels will open and most often it’ll be sodium channels
1 - unbalanced charges distrubuted across the plasma membrane that are repsosnbile for membrane potential
2 - triggering event opens ion channels, most commonly permitting net Na+ ENTRY
3 -
RMP is -70mV
but now becomes -65mV so a small depolarization is produced
The spread of graded potential requires energy
A
True
B
False
B
False
because it is a passive
CHARACTERISTICS OF GRADED POTENTIALS
1 - current loss across the membrane
15mV potential has been created
loss of charge means
K+ leaves and not Na+ because the membrane is more permeable to K+ because there are more K+ leak channels
numbers refer to the local potential in mV at various points along the membrane
Graded potentials die out over short distances
like ripples in the water
CHARACTERISTICS OF GRADED POTENTIALS
Graded potentials can undergo summation & initiate action potentials
-50mV is the threshold potential, when the membrane potential reaches this potential of -50mV, an action potential will be generated
The excitatory presynaptic inputs generate a depolarization
The inhibitory presynaptic inputs generate a hyperpolarization
graded potential can add onto each other to generate a bigger trigger
no summation
- the graded potential is too low to reach the -50mV threshold
spatial summation
- a summation in space
- two different neurons combine to create a threshold potential
EPSP-IPSP cancellation
- an excitatory stimulation is canceled out by the inhibitory stimulation
graded potentials are needed because
a small amount of urine generates a small graded potential, but when it is full it will cause an action potential and now we use the restroom
ACTION POTENTIALS
Brief, rapid, large changes in RMP: inside becomes more positive!
- very brief
DIFFERENT FROM GPs:
- Magnitude & duration always same: 1msec
- Do not die; serve as long-distance signals
after the AP, there is a hyperpolarization then it goes back to the RMP which is -70mV
ACTION POTENTIALS
Arise due to changes in membrane permeability to ions due to conformational changes of voltage-gated sodium and potassium channels
voltages gated ion channels can change their conformation (shape) to either open or close because of changes in the RMP
VG Na+ channel
- has two gates: activation and inactivation gate
open (activated)
closed and not capable of opening (inactivated)
VG K+ channel
- has one gate: activation and inactivation gate
closed
- K+ cannot leave the cell
open (activated)
- when K+ can leave the cell
ACTION POTENTIALS
below threshold potential
- Activation gates closed
with action potential
- Activation gate of VGSCs open
- VGSCs activation gate closed, inactivation gate open
at the top of the AP
- The inactivation gate of VGSCs close
- Activation gate of VGPCs open
on the decline of the AP
- VGSCs activation gate closed, inactivation gate open
- Activation gate of VGPCs close
- Na+-K+-ATPase restores balance
+61mV
know the conformation at the different parts of the AP
trigger for AP
- opening of the VGNa+ channels
CHARACTERISTICS OF ACTION POTENTIALS
Once initiated, AP is conducted throughout the axon
Contiguous conduction in unmyelinated neurons
the axon hillock has the most # of VGNa+ channels which is where the AP is generated
activate area at peak of action potential
the adjacent inactive area into which depolarization is spreading; will soon reach the threshold
the remainder of the axon is still at resting potential
the previous active area returned to resting potential; no longer active; in the refractory period
CHARACTERISTICS OF ACTION POTENTIALS
Action potentials are propagated in one direction only towards the axon terminal, always moving forward
forward current flow excites new inactive area
backward current flow does not reexcite previously active area because this area is in its refractory period
forward current flow excites new inactive area
REFRACTORY PERIOD
VGSCs are closed and not capable of opening the stage
VGSCs are closed and capable of opening stage
VGPCs are open
relative refractory period
- the VG Na+ is in a closed by capable… umm
if at -70mV but what to get to -50mV, then you need a response of 25mV
action potential movie
1 - a depolarizing event brings the resting membrane potential (-70mV) up to the threshold of -50mV
2 - at this time, the voltage-gated sodium channels open
3 - Na+ moves down its electrochemical gradient into the cell making the cell more positive
4 - the inward movement of sodium leaves behind the negative charge with which the Na+ was paired. The membrane continues to depolarize as the inside of the cell becomes more and more positive and the outside more negative
5 - depolarization continues until 0mV is reached
6 - the inward movement of sodium reverses the potential and the inside continues to become more positive until the AP reaches the peak
7 - at the peak, the Na+ inactivation gates begin to close and the K+ gates begin to open
8 - K+ flows down its electrochemical gradient out of the cell making the cell less positive and outside more positive. This leaves behind the negative charges with which the positive charges were once paired inside the cell
9 - membrane potential drops to zero mV. Continual outward movement of K+ begins to restore the resting membrane potential
10 - at resting potential, the Na+ inactivation gates open and the activation gates close
11 - K+ continues to flow out and thus hyperpolarizes the membrane
12 - the K+ gates close and the cell returns to resting membrane potential of -70mV
characteristics of graded potentials
- occur by passive current flow in all directions (unlike AP)
- die out over short distances
- proportional to the magnitude and duration of the stimulus
- they are small changes in the RMP either in the positive direction (depolarization which decreases the potential) or in the negative direction (hyperpolarization which increases the potential
- can undergo summation & initiate AP
types of summations for graded potentials
no summation - both of the stimuli have little effect on the potential
temporal summation - the stimuli stack on top of each other
spatial summation - the stimuli are spaced out and are added together
EPSP-IPSP - excitatory stimuli are canceled out by inhibitory stimuli
what are action potentials & are they the same as graded potentials
APs arise due to changes in membrane permeability to ions due to conformational changes in voltage-gated sodium and potassium channels
- so because the ion channels change shape, the membrane gains permeability for the ions and allows for an action potential!
APs are different from GPs because their magnitude and duration are always the same: 1msec
- while GPs magnitude and duration depend on the stimulus!
APs also do not die but serve as long-distance signals while GPs do die out over short distances
what are the types of conformations of the voltage-gated sodium channels and the voltage-gated potassium channels?
how does this affect an AP?
voltage-gated sodium channels
- closed by capable of opening: the inactivation gate is moved out of the way from the inner cavity and the activation gate is closed
- open (activated): the inactivation gate is moved out of the way from the inner cavity and the activation gate is open! This is a rapid opening triggered at the threshold :) so it is triggered when the threshold of -50mC is reached. So when the AP goes up from the RMP
- closed and not capable of opening (inactivated): the inactivation gate is blocking the inner cavity and the activation gate is open
Slow closing is triggered at the threshold, so when the AP comes back down
voltage-gated potassium channels
- closed: the inner cavity is closed
- open: the inner cavity is open! Delayed opening triggered at the threshold
An AP is triggered when the membrane has permeability for the ions due to the conformational changes ^^^ of the membrane
the conformations of the voltage-gated sodium and potassium channels when an
AP is generated
at RMP:
- both of the sodium and the potassium activation gates are closed
at -50mV which is the threshold :)
- activation gated of the voltage-gated sodium channels open
at the peak of the AP
- inactivation gate of the voltage-gated sodium channels closed
- activation gate of voltage-gated potassium channels open
at the -50mV
- voltage-gated sodium channel activation gate closes and its inactivation gate open
at the RMP (-70mV)
- the voltage-gated potassium channels
activation gate close
Na+/K+ ATPase restores balance
CHARACTERISTICS OF ACTION POTENTIALS
- once initiated, AP is conducted through the axon
- continuous conduction in unmyelinated neurons
- APs are propagated in one direction only (while the GPs are in all directions
REFRACTORY PERIOD
voltage-gated sodium channels are closed and not capable of opening (the inactivation gate is blocking it but the cavity is open)
voltage-gated sodium channels are closed and capable of the opening stage
VGPCs are open
absolute refractory period is where the AP is and also where the membrane has the permeability for Na+
relative refractory period is where the membrane has the permeability for K+
NEURONAL COMMUNICATION
- Short range, released by electrical signals
- Diffuse to act on target cells (gland/neuron/muscle)
SIGNAL TRANSDUCTION
Chemical messengers: lipid-soluble or water-soluble
- Signal transduction process: → message (signal) is “transduced” inside the cell by “transducers” (convert one form of energy to another e.g., radio/phone)
- Lipid soluble: cross membranes → affect gene transcription → affect activity of proteins
- Water soluble: do not cross membranes, bind to receptors → transduce signal inside the cell
– 1st Messenger-receptor binding → intracellular events: - By opening/closing ion channels allowing ions to move in/out
- By transferring the signal to the intracellular 2nd messenger
SECOND MESSENGER PATHWAYS
The message is “relayed” inside the cell via 2nd messenger
- 2nd messengers relay it further to other IC proteins
- Signaling cascade amplifies the initial response
- Major ones: – Cyclic AMP
– Ca2+/DAG - Others exist!
- Disturbances lead to disease
MEMBRANE POTENTIAL
PM is polarized electrically = membrane potential
– Separation of opposite charges across the membrane due to differences in the relative number of cations/anions
