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Cell membrane
phospholipid bilayer where lipid-soluble molecules and gases can diffuse easily, but NOT water-soluble molecules
simple diffusion
small lipid-soluble molecules and gases pass through phospholipid bilayer or through pores
goes down concentration gradient - from HIGH CONC to LOW CONC
facilitated diffusion
no ATP required as it moves down the conc gradient
requires carrier proteins
down the concentration gradient
what are carrier proteins?
structures where solute binds to the transporter, causing a conformational change in the transporter → causes opening of one end and closure of previous end
there’s a LIMITED # OF TRANSPORTERS so transporter system will saturate when conc of molecule exceeds # of available transporter proteins
active transport
movement against concentration gradient
requires energy derived from ATP hydrolysis
uses ion pumps (ATPases)
secondary active transport
movement against concentration gradient
uses energy stored in electrochemical gradient, often from primary active transport
ligand-gated channels
membrane proteins that open in response to the binding of a specific ligand (chemical agent), allowing ions to flow across the membrane
voltage-gated channel
membrane protein that opens in response to change in voltage across the membrane
vesicles
small membrane-bound sacs that transport materials within cells and to the cell membrane
exocytosis
moving from inside to outside
fusion of vesicles with membrane and released
used to release neurotransmitterse
exocytosis 1: “Kiss and Run”
release of vesicle contents occurs through a transient fusion pore that then rapidly re-closes to pinch the vesicle back off from the membrane
voltage sensing mechanism
in the S4 segment of the protein
S4 sticks out to the side of the protein, like a wing
when membrane is polarized, positively charged wing is attracted downwards to negatively charged inner surface of membrane
depolarization of membrane to -50mV can no longer hold S4 wing downwards, so it migrates up → allows ions to diffuse through it
pore loop
creates selectivity filter so that only specific molecules can diffuse through
depends on size AND charge
how often does exocytosis 1 happen before a vesicle is depleted?
occurs several times before vesicle is depleted because only parts of the contents are emptied in one ”kiss”
exocytosis 2: full exocytosis
high levels of signaling
release contents of vesicles all at once by fusing with membrane
What disadvantage comes with exocytosis 2?
complete fusion with membrane can lead to loose membrane (think grandma’s skin)wha
what process counteracts exocytosis 2?
Endocytosis - pinching of cell membrane to create vesicle (brings cellular material into cell)
What 2 conditions must be met to generate a membrane potential?
1) create concentration gradient - enzyme ion pump must actively transport to create concentration gradient
2) semi-permeable membrane - allows one ion species to diffuse across membrane more than others
Na+/K+ pumps
3 Na+ ions pumped out and 2 K+ ions pumped in
THIS is what generates concentration gradient
resting membrane potential
-70mV for a typical neuron
what channel is open at resting MP?
K+ leaking channel is open → K+ can leak out of membrane across the concentration gradient
makes membrane more negative on the inside
what is the main source of resting MP?
Leaking K+ from the K+ leakage channelcreates a negative internal environment.
electrochemical equilibrium
no net movement of ions across the membrane due to equal opposing forces of concentration gradient and electrical gradient
buildup of + charge on the outside repels diffusion of K+
equilibrium potential
electrical work to repel outward cation diffusion equals chemical work of diffusion down concentration gradient
forces are equal in magnitude but OPPOSITE in directionThis is the voltage at which there is no net movement of ions across the membrane, typically calculated using the Nernst equation.
what equation calculates the equilibrium potential?
Nernst Equation
-90 mV is equilibrium for K+ - this means if K+ channels were open and nothing else, it would want membrane potential to be at -90 mV
describes the balance between the chemical work of diffusion with electrical work of repulsion
what counteracts K+ leaving the cell?
the influx of Na+ counteracts K+ leaving the cell and makes the membrane slightly more positive
Na+ equilibrium potential
+60mV
At rest, membrane is not very permeable to sodium but under certain circumstances, permeability can be dominant and there will be net movement of Na+ into the cellwha
what happens when Na+ channels are open?
Na+ diffuses into the cell along the concentration gradient and the inside of the cell becomes more positive than the outside, leading to depolarization of the membrane potential.
Na+ channels
opens in response to depolarization to -55mVthre
Threshold potential
the critical level of depolarization that must be reached for an action potential to be initiated in a neuron
How does Na+ move from outside the cell to inside?
Change in MP allows for S4 segment wings to move upward, allowing Na+ ions in
The MORE depolarization, the MORE Na+ channels open → leads to rapid depolarization
When does the inactivation gate inside the Na+ gate close?
Closes shortly after the channel opens and prevents further influx of Na+ ions, which is crucial for the repolarization phase of the action potential.
What ion channel is needed to generate an Action Potential?
When Na+ channel opens, membrane is depolarized and MP surges towards the equilibrium potential for Na to initiate an action potential.
When does the MP reach +60 mv?
Never reaches because inactivation gates close, meaning no more Na+ comes in to depolarize. Only K+ leakage channels are activated so lots of K+ leaves the cell
Subthreshold stimulus
stimulus that causes depolarization LESS than 15mV
some channels open but not enough to overcome the K+ channels
Threshold stimulus
Enough depolarization to generate AP
aka enough Na+ channels are open
Suprathreshold stimuluss
causes MORE than enough depolarization and produces an AP
Frequency coding
The process by which the strength of a stimulus is represented by the frequency of action potentials
aka higher frequency means stronger stimulus
What is a refractory period?
When a neuron is unable to fire another AP due to the inactivation of Na+ channels after an AP has occurred
What happens during the refractory period?
Channels reconfigure to their original state and membrane becomes excitable againA
Absolute Refractory Period vs Relative Refractory Period
Absolute: ALL voltage-gated Na+ channels are inactivated
no stimulus can generate an AP
Relative: SOME channels are reconfigured
Na+ channels restore themselves at different speeds so some will reconfigure faster than others
can generate a small AP
some Na+ channels are reconfigured and becoming active
Depolarization block
Depolarization that results in permanent Na+ inactivation and membrane remains in absolute refractory state
After-hyperpolarization
The phase following an action potential where the membrane potential becomes more negative than the resting potential
Passive current vs Action Potential
Passive current: current that flows through membranes without generating an AP and weakens with distance
Active Potential: a rapid change in membrane potential that constitutes the electrical impulse along neurons
Impulse conduction
AP propagates from its original site to adjacent patches
Excitable cell
A cell that can generate APs due to change in membrane potential
Neurons are the excitable cells that conduct impulses
What does lambda measure?
Length constant to determine how far we can carry the signal before it dies off
the better the lambda, the longer the potential differences will be carried out without losing from its original value
Conduction speed of AP depends on lambda
What reduces the amount of current lost?
1) Increasing diameter of an axon (wider straw is better)
2) Increasing membrane resistance (wrap straw w/ tape)
What are the 3 things lambda depends on?
Ri - internal resistance
Ro - extracellular fluid resistance
Rm - membrane resistance
What does myelination do?
Increases conduction velocity (think wrapping straw w/ tape so juice doesn’t leak out)
only 20% of cells are myelinated because myelination takes up a lot of space
What are glial cells?
Schwann cells and oligodendrocytes are specialized glial cells that produce myelin sheets to wrap around axons → results in increased membrane resistance and reduces leakage of current out of the membrane
What are Nodes of Ranvier?
gaps between the glial cells where the AP Is generated
Current can cross the membrane at Node of Ranvier
this is where the voltage-gated Na+ channels are located, which helps generate an AP
What happens if there’s no myelination?
Slowing down of signals between the brain and the body, which can lead to diseases like MS where there are issues in fine-motor control
What is saltatory conduction?
AP jumps from one node to the next
ex. Node 1 current strong enough to generate threshold in the next 5-10 nodes to fire an AP
Furthest node will serve as the depolarizing force for the next few nodes
Think student passing messages on in a line and the same message is being passed on
Passive transmission
Electrical signals being transmitted without a new AP being generated
Think students in a line and first student yells so the last student will hear it the least loud
Unmyelinated axons
No myelin sheath → lots of current leakage and slows down conduction velocity
Remak bundle
Non-myelinating Schwann cells that surround unmyelinated axons
What happens at an axon terminal?
AP continues all the way to the axon terminal and releases contents of vesicles via exocytosis
What happens during a refractory period?
AP cannot be regenerated because Na+ channels are all inactivated
Which direction does AP go?
Only goes forward toward the axon terminal - region behind is undergoing refractory period so AP cannot be fired
Synapse
The synapse forms the functional association of a neuron with another neuronE
Difference between electrical synapse and chemical synapse
Electrical: signal transmitted directly from 1 cell to the next WITHOUT release of neurotransmitter
Chemical: depolarizing current results in the release of neurotransmitters into the synapse
Acts as the processing station - neurotransmitter does not always release
What triggers the release of neurotransmitters at the axon terminal?
Influx of Calcium ions
depolarization opens voltage-gated Calcium channels and calcium diffuses into the bouton to trigger vesicle exocytosis
Vesicles are usually docked and lined up with the membrane but with calcium, it triggers the vesicle to fuse with external membrane to release contents into the synapse