Neurophysiology II: action potentials & synaptic transmission Flashcards
Ohm’s Law:
Movement of a dissolved, charged particle across a lipid membrane depends on:
1) The charge of the particle.
2) The difference in distribution of charges across the membrane-this separation in charges is represented by voltage.
-Voltage is a type of potential energy=> how much work is takes to move a charged particle through an electric field.
3) The permeability of the membrane to the charged particle.
I= current: number of charges or charged particle that move across the membrane
V= Voltage: energy generated by separating charges.
R= resistance: more channels =less resistance
Nernst potential:
Membrane potential at which the inward and outward movement of an ion through a channel is balanced and equal:
1) A balance is reached between:
-The diffusional force (movement of an ion down a concentration gradient)
-The electrical force (attraction or repulsion based on the charge across the membrane)
2) Diffusional forces and electrical fields are very small at large distances:
-The nernst potential describes movement of an ion very close to the cell membrane, across channels in that membrane
3) It does not include the flow of ions (current) or the resistance of the membrane to flow…
-Describes energy gradient
Describes the voltage across a membrane that is permeable to X given the ratio of [X] inside:outside
At rest, neurons typically have a membrane potential that is close to the nernst potential for ______.
K+
-75mV: reflects the high intracellular concentration of K+ relative to the extracellular concentration
Due to high permeability to K+ across the neuronal membrane at rest
At rest, the only ion channels that are open are the K+ channels; “leake” channels because they are always open
True or False: If the membrane potential is close to the Nernst potential of a particular ion, it usually means that the membrane is more permeable to that ion.
True
The membrane potential is about -75 mV in many neurons. However, the nernst potential for potassium is close to -90mV.
Why is the membrane potential of a neuron close to, but not the same, as the equilibrium (Nernst) potential for K+?
Due to complex interplay of multiple ions, selective ion channel, and active transport mechanisms that exist in neuronal membranes.
1) Selective ion permeability
2) Sodium-potassium pump
3) Leak Channels
4) Action potentials
5) Other ions and factors
The potential across a membrane depends on _______________________ and the _______________ of the membrane to each ion.
Concentration gradients & the permeability
When the membrane is permeable to more than one ion, then then _______________________________ is necessary to predict the membrane potential.
Goldman field equation
Membranes are poorly permeable to _____________________-movement of an ion across the membrane is dependent on the presence of ___________.
Charged particles; Channels
-Pores in the membrane that allow movement of an ion
-Most channels are selective to relatively few ions: Those ions typically have the same charge
Channels are often dynamic:
They can open and close in response to a variety of stimuli
(membrane permeability & membrane potential can change very quickly)
Channels will change their open/closed states depending on what they’re “built” to detect.
1) Voltage: Voltage-gated channels
2) Stretch or mechanical deformation: mechanoreceptors or osmoreceptors
3) Intracellular messengers
4) Extracellular messengers: ionotropic receptors;
-A ligand binds to a receptor which is also a channel-binding opens the channel, and allows an ion across the membrane
What areas of the neurons do action potentials occur?
Axon (nodes of ranvier), axon hillock, and synaptic terminal: posses large population of sodium voltage-gated channels (Na+ VGC)
-K+ VGC are also present here; they quickly terminate the action potentials
An action potential:
-requires the presence of sodium voltage-gated channels (or sometimes calcium voltage-gated channels)
-Relies on positive feedback
-Always results in a membrane voltage change that is the same size
-Occurs very quickly-The membrane becomes more positive (depolarized) in a matter of milliseconds
Which step of action potential is being described:
- The Na+/K+ ATPase uses ATP to pump Na+ out f the axon and K+ in
-K+ is high inside the axon , so it diffuses out
-Membrane becomes negative inside the axon
-The attractive force of the negatively charged membrane balances out the diffusional force driving K+ out
1) The resting membrane potential
(K+ is higher inside the axon and low outside)
[Balance establishes resting membrane potential at about -70mV (inside membrane is negative)]
Which step of action potential is being described:
-The inside of the axonal membrane becomes more positive, and a Na+ VGC opens
-Na+ VGC opening leads to other Na+ VGC opening, eventually all opening
-Inside of the axon becomes completely depolarized
-K+ VGC open, Na+ VGC close after ~1msec
2) Depolarization
(Channels are open by more positive charges inside membrane)
Threshold=membrane potential at which all Na+ VGC will end up opening (~-55mV)
*Positive feedback, Na+ diffuses into the cell, making membrane more positive, allowing more Na+ in.
Diffusion gradient (high Na+ outside, low inside) as well as electrical force (inside negative) drives Na+ into the cell
Which step of action potential is being described:
-Na+ VGC are closed, no further Na+ entering the axon: after about 1msec/are unable to open for 1-2msec “locked” (will unlock but only if membrane potential repolarizes (inside becomes more negative)
-K+ rapidly leaves the axon: high K+ inside axon and + charge inside the membrane drive K+ out
-Na+ VGC are ready to re-open; when membrane potential is -70mV-after they are “unlocked”
3) Repolarization
(K+ VGC and regular K+ channels are both open, allowing rapid K+ exit)
-
The sodium voltage gated channel has 2 gates:
1) Activation gate: this gate opens as soon as the threshold is reached (membrane depolarizes to -55mV)
2) Inactivation gate: this gate closes very soon after the activation gate opens, after Na+ has rushed into the cell
-Will not open again unless: 1-2msec have passed since it “locked” or cell membrane becomes inside negative (repolarized) again
The potassium voltage gated channel does not have an inactivation gate:
it opens when the cell depolarizes, and closes once the cell is inside-negative again
(slower to open than Na+ VGC)
Absolute refractory period:
Inactivation gate of the Na+ VGC is closed
Another action potential is impossible until this gate opens.
Relative refractory Period:
-Inactivation gate is open, activation gate is closed.
-The cell is hyperpolarized: The membrane potential is lower than resting membrane potential
-A larger stimulus is necessary to reach threshold
Properties of action potentials:
1) All or none events: Begin with a threshold voltage (15mV positive to resting potential) reached
[There are no small or large AP’s, they all involve maximal depolarization=> all Na+ channels open when threshold is reached]
2) Initiated by depolarization
3) Have constant amplitude: Information is coded by frequency, not amplitude; stays the same size no matter how far it travels down the axon
4) Have constant conduction velocity along a fiber: Large diameter conduct faster than small diameter fibers.
-Myelinated fiber velocity= diameter (um)x4.5 m/s
-Unmyelinated fiber velocity= square root of diameter (um)
Saltatory conduction:
“jumping”
-In a myelinated axon, the nodes of ranvier are the only parts of the axon expressing voltage-gated channels.
-The parts in-between are myelinated, and therefore insulated: Insulation allows the electrical field from the depolarization to “Jump” to the next node of ranvier [This is a very fast process]
-The portions of rhe myelin do not experience action potentials-they can’t, there’s no ion channels and myelin keeps ions from crossing the cell membrane: Therefore it’s the positive “electric field” from one node of ranvier that brings the next node of ranvier up to threshold.
Basics of synaptic transmission:
Calcium entry is mediated by opening of Ca+2 VGC:
-Not from intracellular store release
-The whole point of the action potential is to open Ca+2 VGC in the presynaptic terminal => Ca+2 induced exocytosis of NT into the synaptic cleft
Steps of vesicle release:
1) v-SNARES and t-SNARES “zipper” together:
-Synaptotagmin and complexin prevent premature fusion and release after zippering
2) AP=> depolarization=> Ca+2 VGC opening=> calcium influx into the pre-synaptic terminal
3) Calcium binds to synaptotagmin=> disengagement of complexin
4) The synaptic vesicle fuses when complexin disengages => release of NT into the synapse
5) The v-SNAREs and t-SNARES disengage, and the vesicle is re-used
-This occurs after intracellular calcium levels decrease.
The toxins produced by clostridium botulinum are some of the deadliest known:
They impair the assembly and function of v-SNAREs and t-SNARES:
-This impairs fusion of vesicles with the presynaptic membrane
Used therapeutically (in tiny doses) to reduce muscle spasticity, treat migraine…and decreases wrinkles:
-Prevents release of acetylcholine from motor neuron pre-synaptic terminals, which is necessary to excite contraction in skeletal muscle
7 main types of botox: medical applications use Botox A:
-Botox A binds to SNAP-25, a v-SNARE
Neurotransmitters don’t stay bound to receptors forever:
-Degraded by enzymes in the synapse:
ex) acetylcholinesterase degrades acetylcholine to acetate and choline
-Reabsorbed by nearby astrocytes
-Reabsorbed by pre-synaptic terminal
-Diffuse out of the cleft and carried away by blood
Many metabotropic receptors are linked to G-protein signaling:
Only need to know bold and underlined neurotransmitters.
True or False: Even if an EPSP is higher than threshold, no AP will occur unless Na+ VGC are present.
True
[graded potentials can vary in size]
Summation:
If multiple EPSPs from different sites(say points 1 & 2) meet at the same time, same place on the membrane => spatial summation
Graded potentials last longer than AP: If multiple graded potentials add up in a “staircase” fashion over time => temporal summation
(seen at point A in the diagram)
Many different axons synapsing on one neuron can result in a wide array of ________ & ________
EPSPs & IPSPs
They can be long or short lasting, depending on the receptor and how many APs are being sent per second.
The net result of all these EPSPs & IPSPs can be integrated at the axon hillock.
(if the graded potentials bring the hillock to threshold => an action potential (or string of action potentials, if the graded potential lasts many milliseconds))
Every neuron is a complicated ____________ integrating the inputs from all of the neurons that it synapses with, and making a _________ as to whether those inputs are enough to bring the axon hillock to threshold.
Computer; decision
We have 10^11 neurons w/ thousands of dendritic spines (and synapses) per neuron
Chemical synapses and graded potentials add an extra level of complexity
Metabotropic receptors can have very long-lasting effects that include protein synthesis and long-lasting intracellular signals
Graded potentials vs. action potentials chart =>
