Lecture 18: Intro to Neurophysiology & Membrane Potentials Flashcards
What is Fick’s Law’s equation?
Ji = Di.A . (C1-C2)/ x
- Ji = flux/mvt of substance i between 2 compartments via simple diffusion
- Di = diffusion coeff for the specific ion (which includes the partition coefficient)
- A = area over which diffusion takes place
- x = distance = membrane thickness
- C1-C2) = concentration gradient
What is Fick’s Law’s equation for the diffusion of an ion between the exterior and interior of the cell?
Jx = Px . (X0-Xi)
Px = permeability coeff
X0 = concentration outside the cell
Xi = concentration inside the cell
What is the permeability coefficient Px specific to? What is it affected by?
- Specific for a given molecule/ion
- Affected by # and type of channels that the ion can pass through
What does the permeability coefficient Px combine?
- Lipid/water partition coefficient (whether the ion prefers to be in lipids or water)
- Diffusion coefficient
- Membrane thickness
- Standard 1 micron squared area
What are gated channels?
Channels that can be open/closed by chemical, voltage, light, or mechanical forces
What are 3 names that non-gated channels are referred to as? What are they specific too? Can these be open/closed?
- Pores
- Passive channels
- Leaky channels
⇒Specific to ions
NOPE, they are always OPEN!
How does an increase in temperature affect the diffusion coefficient and the permeability?
It increases both
What are the 2 resting properties of the cell?
- Membrane resistance
- RMP
What channels are important in determining the resting properties of the cell?
Leaky channels
What is Jmax?
The max movement of ions due to the limited number of channels (traffic jam)
Can Jmax be attained physiologically?
NOPE
What is the electrical equivalent of ion channels?
Battery in series with variable resistor
What is the equation for Ohm’s Law?
V = R.I
What is the equation for conductance?
G = 1/R
What is the equation for current?
I = G.V
What electrical properties do all channels control?
Resistance and conductance
What electrical property does permeability refer to? What is the slight difference between the 2?
Conductance
Difference: permeability is the ABILITY of an ion to move across a membrane and is dependent on the # of channels VS conductance is an actual electrical measurement of the movement of ions (flux)
⇒ you cannot have conductance without flux of ions = current
What is conductance dependent on in an ion channel?
The amount of current that can flow through: intrinsic property of the channel
What is the unit of resistance?
Megaohms
What is the unit of conductance?
Picosiemens or nanosiemens
What is the unit of voltage?
mV
What is the unit of current?
Nanoamperes or picoamperes
How many subunits does a typical voltage-gated channel have?
4
What are Na+ voltage-gated channels similar to?
Ca2+ voltage-gated channels
What part of the voltage-gated channel acts as the selectivity filter? How does this work? Where is it located?
P-loop: negatively charged to let positively charged ions through
Strategically placed at the interface between different subunits of the channels
What is the electrochemical equilibrium?
The equilibrium reached when electrical forces and concentration differentials stabilize and the movement of ions in = movement of ions out
What causes a voltage across a membrane?
A charge differential
What equation determines when the electrochemical equilibrium is reached? What does it provide? Write it out.
The Nernst equation: provides the voltage at which an ion is in electrochemical equilibrium given initial concentrations.
EK = 60/z . log ([Kout]/[Kin])
- EK = equilibrium voltage of K+
- z = charge of the ion
Describe the RMP in terms of inward current of Na+ and outward current of K+?
- IK+INa = 0
- IK = - INa
What equation to use to determine the resting membrane potential? Write it out.
The Goldman-Hodgkin-Katz equation
- P: permeability of that ion
What is the difference between electrochemical equilibrium and RMP?
- Electrochemical equil: does not require energy to reach and happens naturally
- RMP: steady state so requires energy (ATP) used by the N+/K+ ATPase
What equation to use to calculate the current of a specific ion through a membrane? Write it out.
Modified version of Ohm’s Law:
I = G . (Vm<span> </span>- Eeq)
- I = current of an ion
- G = conductance
- (Vm<span> </span>- Eeq) = driving force of ion movement = RPM - equilibrium voltage for a given ion
What happens if Vm = Eeq ?
No current for that ion ⇒ membrane potential is at the reverse potential for that ion
What equation to use to calculate RMP AT STEADY STATE when you have the conductances and know the equilibrium constants for each ion?
Conductance equation:
In the electrical circuit analog, what is the driving force for movement of an ion across a membrane?
The difference between the membrane potential and the equilibrium potential for that ion
What are scaffolding proteins?
Proteins that create a frame to help anchor specific proteins to the lipid bilayer
What enables a cell to create an action potential?
It’s able to separate its intracellular composition from the extracellular composition
Where is Cl- concentration higher: inside or outside the cell?
OUTSIDE
What is the effect of channels on the permeability of the membrane?
Increase permeability coefficient
What is the rate at which Na+, K+, and Cl- can cross the membrane?
106 ions/sec
What are ligand-gated channels?
Channels that need a ligand to bind to be activated
What are water channels?
Aquaporins: control osmotic movement of water
What controls the selectivity filter of the voltage-gated channels?
Voltage sensor that senses changes in voltage to activate the voltage-gated channel
Is it possible to have an inactivated voltage-gated channel when there is a voltage being experienced?
Yes
Describe the composition of the voltage-gated channels.
Water-filled pore and group of AAs that loosely bind the ion
How
How many subunits does a ligand-gated channel have?
5
How many subunits does a gap junction have?
6
What is the fifth red segment on a hydropathy plot?
The pore domain: where ion permeation takes place
What is the permeability ratio?
The ratio of channels
What is the permeability ratio of the K+/Na+ channels in a neuron cell?
100:1
What is the equilibrium potential of K+?
-58mV
What is the equilibrium potential of Na+?
+60mV
-58mV
What do to with the Goldman-Hogkin-Katz equation when one of the ions cannot pass through the membrane?
Take it out of the equation!
What does it mean for a pump to be electrogenic?
It hydrolyze ATP to transport ions across biological membranes leading to the translocation of net charge across the membrane (eg: 3 Na+ for 2 K+)
What is considered positive current?
Current going out of the cell = positive outward current
What is considered negative current?
Current going into the cell = inward negative current
What kind of current makes the cell depolarize?
Negative inward current
What kind of current makes the cell hyperpolarize?
Positive outward current
What is capacitance? How do you calculate it?
Ability to store charge
C = Q/∆V
- Q = charge (in Coulomb)
- ∆V = change in voltage
What is the unit of capacitance?
Farad
How to vary the capacitance of a capacitor?
Increasing the distance between the plates of the capacitor: decrease capacitance
How does permeability relate to membrane resistance? Conductance?
High permeability = low membrane resistance = high conductance
What kind of ion movement through membrane channels? What is the exception?
Facilitated diffusion with transport maximum
Resemble simple diffusion except at Jmax
Describe the structure of ion channels.
Mutiple subunits with distinct transmembrane segments.
What type of channels does a glial cell have?
K+ channels only
What does the RPM refer to?
The electrical potential of the inside of the cell
Can an ion that is not permeable to a membrane affect the membrane’s RMP?
Not technically, but calcium is special in that way
How can one measure the permeability, G, of an ion?
Slightly increase or decrease the concentration and see if the membrane potential changes because V=G.E (E depends on concentration):
- If it does: ion is permeable
- If it does not: ion is not permeable
How does the flux of K+ relate to the flux of Na+ at steady state?
INa+ = - IK+
If the ion channels were included on an electrical circuit, would they be in series or parallel? What constitutes the generator?
Parallel
Na+/K+ pump
Why does it take time for the voltage to attain its max and back to min? How is this measured?
Because of capacitance! Time constant = amount of time it takes to charge and discarge the membrane capacitance
Time constant = Rm . C
- Rm = membrane resistance
- C = capacitance
What does the time constant conceptually mean for the capacitor?
- At time t, the charge on the initially charged capacitor is 63% of its max value
- At time t, the charge on the initially charged capacitor is reduced to 37% of its max value
What is the slope of V vs I?
Conductance, G
Write out the conductance equation when GNa = GK?
Vm = (ENa+ EK) / 2
What is the role of the Na/K-ATPase pump? What would happen without it?
To make sure concentration gradients are maintained.
Without it concentration gradients would disappear over days.
If the ratio of Na+:K+ pumps is 1:100, when will the effect of the Na+ pump be the greatest?
When [K+] is low
What represents the capacitor in a cell?
Membrane lipids are the insulator and the 2 ion containing solutions on either side are the parallel plates
What does the time constant mean for conduction velocity?
SMALL TIME CONSTANT = FASTER VELOCITY
What does the space constant mean for conduction velocity?
LARGE SPACE CONSTANT = HIGH VELOCITY
How is the partition coefficient affected by hydrophobicity and hydrophilicity?
Higher if hydrophobic
Lower if hydrophilic
Why is RMP closer to that of the EK+?
Because there are more K+ leaky channels than Na+ leaky channels
How does permeability affect the GHK equation?
Higher permeability = more ion channels = larger effect on Vm
What are the 4 common properties of ion channels?
- Amount of current that can flow: depends on the voltage applied and an intrinsic property called “the conductance” that is the inverse of resistance.
- Mean open time: how long the channel stays open on average
- Frequency of opening: how long are the average closing intervals are
- Selectivity of the channel for ions: determines which ions flow through
Describe the effect of capacitance on current.
It minimizes the number of ions that move for each voltage change across the membrane
Describe the movements possible/impossible in a phospholipid bilayer.
Translational mvt: possible
Lateral mvt: impossible
Attached with scaffolding proteins: no movement possible
Why do we say that ion channels propose like hybrids?
They use size and loose interior binding sites to select for ions
Do all ion channels bind ions on their interior?
NOPE
Describe the structure of voltage-gated ion channels.
6 transmembrane helices with the 5th one being the P-loop
Can conductance be negative?
NOPE
By how much can an AP depolarize a cell?
+120 mV
How does cell size affect capacitance?
Increased cell size = increased capacitance
What is the RMP created by and maintained by?
Created by leakage K+ channels and maintained by Na+/K+ ATPase
What does oubain do to a cell? To its RMP?
Inhibits the Na+/K+ ATpase pump
Polarized RMP
What is the difference between equilibrium potential and reversal potential? When are they equal?
Reversal Potential is determined in a voltage clamp experiment as the potential where the current changes direction.
Equilibrium Potential is defined by Nernst equation.
When a current is caried by a single ion (i.e Voltage gated Na channels) the Reversal potential is the same as the Equilibrium Potential for that ion
Does osmosis require aquaporins?
Yes!
Is glycerol lipid soluble?
YUP
What would the RMP be if a cell is only permeable to K+?
-60 mV
