Lecture 3 Flashcards
movement of electric charge movement of electric charge (ions)
electrical current
force exerted on a charged particle
electrical potential
relative ability of an electric charge to migrate from one point to the next
electrical conductance
relative inability of a charge to migrate
electrical resistance
Ohm’s Law
V (voltage) = I (current) * R (resistance)
Equation for conductance
g (conductance) = 1/R
difference between membrane potential (Vm) and the equilibrium potential of a particular ion (Eion )
driving force
ionic current
conductance X driving force (Gion[Vm-Eion])
What are the currents of Na, K and Cl at rest?
- Ina is inward (negative)
- Ik is outward (positive)
- Icl is approximately zero
What changes during an action potential?
- membrane permeability to Na and K
- conductance
- ionic currents
___ current is depolarizing. ___ ions move in and ___ ions move out.
inward
positive
negative
___ current is hyperpolarizing. ___ ions move out and ___ ions move in.
outward
positive
negative
Depolarizing current shows a ____ deflection on a current vs. time chart.
downward
What does tetrodotoxin do?
Blocks sodium current
What does tetraethylammonium do?
Blocks potassium current
activated by the influx of Na +, counteracts the effect of that cation by allowing the discharge of K + (resets the membrane potential)
K+ delayed rectifier channels
During resting potential, potassium channels are ____, and permeability to potassium is ____. Resting membrane potential is near ___.
always open
highest
Ek
During depolarization, permeability to Na+ _____. Membrane potential _____.
increased
rises
Voltage-gated Na+ channels open in response to ________.
depolarization above threshold (~-50mV)
The voltage-gated Na+ channel is a single long polypeptide with __ domains each with __ transmembrane alpha-helices. It is ___ more permeable to Na+ than K+ due to ____.
4
6
12x
hydration (potassium is too big when hydrated)
The __ alpha-helice in sodium channels is the voltage sensor. It twists away from the inside when the cell is depolarized to ___. The twists causes the channel to open and ____. Vm ___ as a result.
S4
-40mV
Na+ to rush in
rises
Following depolarization, Na+ channels become ____. K+ channels, on the other hand, only ___.
inactivated
close
the period immediately following the firing of a nerve fiber when it cannot be stimulated no matter how strong the stimulus; due to the increase in K+ permeability
absolute refractory period
What de-inactivates the sodium channels?
repolarization
What happens during the rising phase of an action potential?
- voltage-gated sodium channels open
- potassium channels close
- sodium influx
What happens during the falling phase of an action potential?
- sodium channels inactivate
- potassium channels open
- cell becomes more negative
4 polypeptide subunits joined to form a pore
voltage-gated potassium channels
What is an afterhyperpolarization?
voltage-gated K+ channels take a few msec to return to the closed state; efflux of K+ from the cell is higher than at rest; membrane potential becomes more negative than at rest
a period during which you can trigger an AP by applying a larger than normal stimulus; some (but not all) Na+ channels have been reset
relative refractory period
What is spatial buffering of potassium and why is is important?
repolarization of neurons tends to raise potassium concentration in the extracellular fluid; potassium ions are taken up at one region of the astrocyte and then distributed throughout the cytoplasm of the cell, and further to its neighbors via gap junctions.
How does lidocaine work?
blocks sodium channel pore (from inside), blocks action potentials in sensory axons so that pain signals do not reach the brain
How does scorpion toxin work?
It blocks sodium channel inactivation –> muscle stiffness
How are action potentials propagated?
Na+ channels locally open in response to stimulus generating an action potential; resulting current flows passively along the length of the axon
Why doesn’t the action potential travel backwards?
upstream Na+ channels inactivate, K+ channels open –> temporary hyperpolarization; also delay in sodium channel reopening
What is membrane resistance (Rm)?
of channels open for ions to cross the membrane
How is membrane resistance related to the surface area of membrane and conduction speed?
- increased SA –> increased leaky channels –> decreased resistance
- increased resistance –> increased conduction speed
How is internal (axial) resistance (Ri) related to axon volume?
increased diameter –> increased volume –> decreased resistance
How is internal (axial) resistance (Ri) related to conduction speed?
decreased resistance –> increased speed
What does myelin do?
acts as insulation to decrease current loss through leak channels
How do the Nodes of Ranvier work?
voltage-gated sodium channels present in nodes only; action potential “recharges” as it propagates
action potential “jumps” from node to node
saltatory conduction
damage or loss of myelin over time
demyelination
myelin never forms correctly
dysmyelination
slowly progressive CNS disease; characterized by patches of demyelination in the CNS
multiple sclerosis
What are the symptoms of MS?
- weakness and clumsiness
- stiffness and gait disturbances
- visual disturbances
- mental disturbances, including lack of judgment, emotional liability, sudden weeping or laughter
What is the epidemiology of MS?
- affects mainly Caucasians
- average age of onset is 28 - 30 years
- female:male ratio = 2:1
- chronic illness leading to cumulative disability
- complex disorder (combination of genes and environment)
- mediated by autoimmune processes
What causes MS?
- myelin proteins recognized as foreign by T cells
- lymphocytes and macrophage cross BBB and destroy oligodendrocytes
- molecular mimicry (?): antigen initiates an immune response, antibodies cross-react with a self protein that “mimics” the antigen
Is is possible to recover from MS?
- occasional re-myelination
- some demyelinated axons express higher than normal densities of sodium channels in demyelinated regions (restore conduction –> remission)
- degeneration of axons is irreversible; permanent loss of function
How is MS treated?
- no cure
- enhance endogenous remyelination
- limit damage to oligodendrocytes
- transplant exogenous myelin-forming cells (stem cells)
