Biological eqivalence of a resistor
ion channels, regulate flow of ions and control electrical signals in neurons
Biological equivalence of a battery
cell membrane potential (or resting), store electrical energy due to uneven distribution of ions across membrane
Cell membraner acts as a __ that can__
acts as a capacitor that can seperate charges to create membrane potential
When is I r zero?
no net flow of ions across membrane (resting) or when membrane is at equilibrium potential for specific ion
When is I c zero?
no change in voltage
what are the 2 configurations of channels?
open or closed
In action potential simulation, the net total current shown to be zero during action potential. Why?
I r (ionic current) is equal and opposite to Ic
T/F: all voltage-gated ion channels are selectively permeable to sodium
FALSE
depending on channel can be Na+, K+, Ca2+
T/F Ion channels are conducting or not conducting
TRUE
either conducting (open) or not conducting (closed)
2 requirements needed for current to flow through ion channel?
1. channel needs to be conducting (open to allow ions to flow)
2. needs driving force (Vm-Eion): difference between membrane potential (Vm) & equilibrium potential for ion (E ion), if there's difference ions move through channel generating current
Positive ions flowing into the cell represent a depolarization/polarization? outward/inward? positive/negative?
depolarization (less neg)
inward (ions moving into cell)
negative (movement of pos ions considered neg current)
In Hodkin and Huxley model, what do a and B represent and what recording technique was used to measure these values?
a: rate constant for channel opening
b: rate constant for channel closing
voltage clamp
What is being measured in voltage clamp technique?
current across membane
similarity and differences of voltage clamp recording and patch clamp single channel recording?
1. Both measure ionic currents & used to control membrane potential of cell
2. voltage clamp records Itotal from many channels (macroscopic current)
3. Patch clamp is single channel recording, measures current through individual ion channels (microscopic current)
How do molecules move across membrane via
a. Diffusion
b. Active transporter
c. Passive transporter
Difusssion: movement of ions from high to low concentration
Active transporter: move against concentration gradient, requiring ATP
Passive transporter: move without energy input (facilitated diffusion)
What determines net transport of molecules in one direction?
depends on energy source which can come from cellular metabolism or electrochemical gradient
How do uncharged molecules behave in terms of concentration?
Uncharged molecs are sensitive to concentrations.
If not equally distributed, they will move to equal concentrations, creating osmotic pressure that drives their movement.
How do ions respond to electrical and concentration gradients?
ion sense electrical and concentration gradients. Nerst equation calcs voltage at which both forces (electrical & concentration) balance
- if ions equally distributed, Nerst potential is zero
- if ion move out = ion move in --> no net movement
What does Stochastic behavior mean in protein conformations
the conformation of a protein can switch between states: open, closed, or random (stochastic). any moment, there's a probability of finding molecules in given state
What happens to net charge movement at the Nernst potential?
At Nernst potential, there is no net movement of charge for that specific ion; the driving forces driving the ion in and out are equal, in a balanced state.
What happens to the zero current potential with the Nernst potential?
Nernst potential shifts the zero current potential from 0V to equilibrium potential of the ion (Eion)
New version of Ohm’s Law when considering ion movement
I ion = Gion (V-Eion)
How do individual currents behave ?
individual ion currents add up to each other, total curent is sum of all ion currents.
What family do voltage-gated ion channels belong to?
large family of proteins that control ion flow across membrane
How are K+ channels structured?
have 6 transmembrane (TM) domains and a pore forming loop between TM5 and TM6. function by forming tetramers (four subunits)
How are K+ and Na+ channels similar and how are they different? Can you can predict from the amino ascid sequence if a protein is a K+ or Na+ channel?
a. K+ and Na+ channels contain multiple subunits, with each subunit consisting
of repeating transmembrane spanning motifs
b. K+ and Na+ channels differ in the selectivity filters, conferring selectivity to K+
and Na+, respectively
c. For example, K+ channels have a signature amino acid sequence that is
highly conserved and forms the selectivity filter
what is TM domain
protein that helps form the structure that let ions pass through membrane
What is pore-forming loop
protein helps create the actual opening (pore) through which ions flow, splits transmembrane domains in 2 and lines the channel to let specific ions pass
What is TM5 and TM6
5th and 6th transmembrane domains of protein
4k Channel like domain?
Na+, Ca2+ is similar to K+ channels. In these channels, there are four k channels like domains that make up full channel, instead of being 4 seperate proteins, Ca2+ and Na+ are part of one single protein rather than 4 seperate proteins coming together.
Which domain vontains the voltage sensor in ion channels?
domain TM4
what is the pore-forming subunit of ion channels called?
alpha 1. most channels have interacting proteins or subunits
How does the behavior of individual ion channels affect the membrane?
The behavior of individual ion channels determines the overall flow of current across the membrane. Current can either charge or discharge the membrane's capacitance, changing the membrane voltage.
What happens when the membrane capacitance is charged or discharged?
charged, voltage across membrane increases. discharge, voltage decreases. opening and closing of individual channels controls process
Besides open or closed what other state can a channel be in?
Inactivatedm similar to desensitization, channel no longer conducts ions even through it may appear open.
What can cause channel inacitvation?
channel blocked by a component of the channel
What are the difference state a channel can have?
Closed: all gates are closed
Closed (partially open): all but one gate is open
Open: all gates open, allowing ion flow
Inactivated: channel technically open but no longer conducting ion flow
How do individual channel behavior add up to create macroscopic current?
summation of individual channels in different states produce macroscopic current, which is total current across membrane.
can you estimate single channel conductance from voltage clamp recordings? If so what would you need to know and measure?
a. yes, you would need estimates for (1) tital # ion channels (2) open probability of those channels (3) equilbrium potential for ion
b. measure total current at given membrane potential
c. input membrane voltage, total current, & equilibrium potential into equation: I ion = G ion * (V m – E ion )
d. input total conductane, channel open probability (n^4) and # channels into following: G ion = n^4 (#channels)(g ion)(N^4 assumes K+ channel)
What are single channel recording good for ?
allwo precise measurements of ion channels opening and closing, gating properties, and conductance
VS voltage clamp measures average activity of Many channels and doesn’t provide single channel resolution of ion channel properties
why are there so many genes in each ion channel family?
enable diverse neuron types to have specialized signaling properties (ex: distinct firing patterns)
why are there so many K+ channels in particular?
K+ channels are critical for generating resting membrane potential
Why provides the voltage dependce of ion channels?
S4 segment (contains positively charged amino acid residues)
How could different properties of voltage gated ion channels influence the duration and frequency of action potentials?
Channel activation and inactivation kinetics: slower kinetics will lead to longer
action potential and lower frequency
b. For example, prolonged sodium channel inactivation will extend the refractory
period and decrease the maximum frequency of action potentials
Why are there so many different types of action potentials?
Diverse channel types
Myelination increases conductance speed of an action potential. Why could this be
important? What happens if myelination is reduced in a demyelinating disorder?
Enables animals to receive quick feedback / respond quickly to sensory stimuli
b. Demyelination results in slowed or impaired conduction of action potentials
and can cause symptoms including motor deficits and muscle weakness (for
example in multiple sclerosis)
22. What are differences in CNS and PNS myelination?
CNS myelination is achieved by oligodendrocytes and PNS myelination is achieved by Schwann cells
V rest
refers to the electrical potential difference across cell membrane when the cell is at rest (not actively recieving signals)
two main factors that constibuted to Vrest
membrane permeability
concentration gradient of permeable ions across membrane
How does concentration gradient affect Vrest
concentration gradient refers to the difference in ion concentration insdie the cell ([X] in) compared to outside ([X] out). this gradient drives the movemement of ions, creating an electrical difference
How does the combination of selective permeability and concentration gradient create Vrest?
cell membrane’s selective permeability allows certain ions to move in or out based on their concentration gradients. This movement of ions results in a charge difference across membrane, creating resting membrane potential (Vrest)
How does increasing the diameter of non-myelinated axons affect the speed of conduction?
increasing diameter increases speed of conduction with the square root of the diameter
How does increasing diameter for myelinated axons affect the speed of conduction?
relationship between diameter and speed of conduction is linear. meaning that as diameter increases, speed of conduction increases at a constant rate
What determines optimal distance between node of Ranvier in myselinated axons?
optimal distance between nodes depends on the size of the(diameter) of axon. larger axons generally have greater internodal distances
what limits the lower end of internodal distances in peripheral axons
schwann cell size limit lower end of internodal distances in peripheral axons. Schwann cells wrap around axon to form myelin sheath, their size sets minimum limit for the distance between nodes
What effect does myelination have on axons?
myelination insulate the axon, whihc increases membrane resistance and decreases membrane capacitance, making electrical signal transmission more efficient
What happens to nodes of Ranvier in myelinated axon?
the action potential is generated. electrical signal spreads passively and very fast through myelinated section due to decreased capacitance.
How does myelination affect the spread of electrical signals between nodes of Ranvier?
The entire segment of the axon between the nodes is depolarized, allowing rapid signal transmission through the myelinated regions.
What cells are responsible for myelination in the peripheral nervous system (PNS)?
Schwann cells are responsible for myelinating axons in the peripheral nervous system (PNS).
What cells are responsible for myelination in the central nervous system (CNS)?
Oligodendrocytes are responsible for myelinating axons in the central nervous system (CNS), and they can serve many axons with a single myelin layer.