Intro to neurons/Resting membrane potential Flashcards
What are the two broad categories of neurons
- Neurons
- Glia
How many neurons in the human brain?
Approx. 86 billion
Neuron structure and function of each part
- Dendrites are inputs. Often there are many. They taper in diameter.
- Soma (cell body) sums all the inputs from the dendrites.
- The axon is the output (only one but it can branch.) Axons have constant diameter.
- Some neurons don’t have an axon or dendrites (but still function as neurons).
Structure of an idealized neuron
Communication within and between neurons
Interactions at Synapses
A neuron isn’t purely pre- or post-synaptic. It can be pre-synaptic to many others and post- synaptic to many others (even itself)
Dendrites
- “trees”
- unique to neurons
Dendrites - most synapses end on dendrites (i.e. dendrites are neuron inputs)
- neurotransmitters bind to special receptor proteins in the cell membrane of dendrites
- ion channels in membrane allow electrical signals to reach soma
Dendritic Spines
- some dendrites are spiny, others are not
- synapses often end on spines
- shape and density of spines determine synapse strength, timing properties, etc
- spines change in development and with learning
Rats: dendritic spine changes associated with environmental enrichment
Humans: dendritic spine abnormalities associated with intellectual impairment
Example 1: general intellectual impairment - long and abnormally spindly spines
Example 2: Fragile X syndrome (most common genetic cause of autism)
- long and abnormally dense spines
Neuron Cytoskeleton
Scaffold proteins affect neuron shape and function (common to eukaryotic cells):
* microfilaments – 5nm
* neurofilaments – 10nm
* microtubules – 20nm (transport
molecules up and down axon)
Microtubule Associated Proteins (MAPs)
Regulate assembly and function of microtubules
e.g. the MAP known as tau protein links microtubules
Alzheimer’s Disease macroscopic pathology
- Cell death, gyri shrink, sulci & ventricles expand
- Cognitive deficits – memory loss, confusion, difficulty with speech and navigation
- Innumerable factors are reported to influence occurrence, but cause is unknown
Alzheimer’s Disease microscopic pathology
Two key proteins are abnormally clumped
- Tau protein forms neurofibrillary tangles inside neurons
(number of tangles correlates with cognitive decline) - Plaques made of β-amyloid protein form outside neurons
Alzheimer’s Disease Progression (β amyloid hypothesis)
- abnormal secretionof βA by neurons; βA clumps into plaques
- βA triggers tangle formation: - shape of tau changes
(excess phosphate molecules attach to tau) - microtubules fall apart - neuron dies
- tau accumulates (tangles)
- distorted tau and βA spread to nearby neurons
Axons
- unique to neurons
- axons have few or no ribosomes (little or no protein synthesis). Needed proteins must come from the soma
- ion channels in the axon membrane are critical for electrical conduction of action potentials
Axoplasmic Transport
Transport of organelles and molecules between soma and synapses along axons
* Anterograde – toward axon terminal
* Retrograde – away from axon terminal
Axoplasmic transport- microtubules
Herpes
- Enters nerve terminal through broken skin → retrograde transport to soma
- Viral replication occurs in soma
- Anterograde transport of HSV causes cold sores recurrence on lips
Rabies
- Enters nerve terminal through bite → retrograde transport to soma
- Viral replication occurs in soma
- Cell death (no anterograde transport)
Glia
“glue”
* Brain is ~50% glia
* Generally small soma, 5 - 20 μm (neuron somas are 5-100μm)
* Roles: electrically insulate neurons, protect neurons from infection, nourish neurons
Astrocytes
- one of the most common glia
- fill spaces between neurons
- regulate ion concentrations around
neurons - guide neurons in development
- protect neurons by taking up toxins
Myelinating Glia
Myelination: Oligodendroglia & Schwann Cells
- Schwann cells are in the PNS (peripheral nervous system) – each insulates about a 100 micron length of a single axon
- Oligos are in the CNS (central nervous system) – each insulates many neurons (up to about 50).
- Why the two types?
Are Schwann cells in the PNS or CNS?
PNS
Are Oligos in the PNS or CNS?
CNS
CNS Tumors
- CNS tumors are generally glia cancers. Most common are astrocytomas (most serious is glioblastoma)
- Why don’t we see neuron cancers?
Rare because neurons don’t generally divide in the adult brain - Symptoms of a glial tumor include nausea, headache, vomiting, and functional deficits associated with the affected part of the brain
Brain electrical activity
Electrical activity of individual neurons
The neuronal membrane at rest
Potential difference in electrical circuits
Potential difference in neurons
Ion concentrations in axoplasm and extracellular fluid mM)
How are the ion concentration gradients established and maintained?
- The sodium-potassium pump! (and other ion pumps)
- It moves 3 Na+ out of the cell and brings 2 K+ into the cell
- The pump runs constantly to establish and maintain Na+ and K+ concentration gradients
- Dysfunction causes various motor and seizure disorders. Complete failure of the pump would be fatal.
The sodium-potassium pump
- The sodium-potassium pump moves ions
against their concentration gradients - This process takes a lot of energy. The brain uses 20% of the bodies ATP (but is only 2% of mass).
- The pump uses about 70% of the brain’s ATP!
Ion channels allow ions to diffuse across membrane
- The cell membrane blocks the diffusion of ions across the membrane
- Ions can cross the membrane through ion channels (and ion pumps)
- Ion channels are composed of proteins that span the membrane (transmembrane subunits)
- Ion channels have a pore that passes the ion (if open)
Selective ion channels
- Some ion channels are “selective”; i.e. they only pass one type of ion
- Selectivity is based on the size of the pore and the subunits the channel is made from
- Most ion channels have two states, open and closed
Ion movement through ion channels is governed by two forces: Diffusion and Electrical
- Diffusion force: ions move down concentration gradients (away from high concentration toward low concentration)
- Electrical force: ions with like charge repel and ions with opposite signs attract
Ions diffuse down concentration gradients through open channels
- Add table salt to water on one side of membrane
- Both Na+ and Cl- channels are open
- Both ions diffuse across membrane down concentration gradients until equal concentrations on both sides of membrane
- When both positive and negative ions diffuse, there are equal numbers of the two on each side of the membrane
When is equilibrium reached?
When diffusion force equals electrical force
Equilibrium
- Na+ diffuses to the right down concentration gradient
- Positive charge builds up on right side and negative charge on left side (bc Cl- can’t cross)
- As Na + diffuses, Vm becomes more negative on the left
- Na+ on right starts repelling the flow of more Na+
- Eventually, electrical repulsion stops the diffusion. At this point, the membrane is in equilibrium.
In reality, the small difference in + and – charges appears right at the cell membrane
- The asymmetry in the number of ions on the two sides of the membrane involves a small percentage of all the ions
- Solutions away from the membrane are effectively neutral
Equilibrium Potential & Ionic Driving Force
What is the driving force of an ion?
The difference between the current membrane potential and the ion’s equilibrium potential
The higher the driving force, the ___ ions will move across the membrane
Faster
When the membrane potential is at the equilibrium potential for an ion, what is the driving force?
0
Equilibrium Potentials of Important Ions
The greater the concentration gradient, the ___ Eion is away from zero (for ions with same valence).
Greater
Driving force at resting membrane potential
Driving force at different membrane potentials (table)
At a low negative membrane potential (typical resting potential), the driving force is much higher on ___ than on ___
Much higher on Na+ than on K+
At positive membrane potentials the driving force becomes higher on ___ than on ___
Higher on K+ than on Na+
For a positively charged ion, a positive driving force means ___ and a negative force means ___ (easy to remember with salty banana)
Outwards, inwards
How is equilibrium the point Eion determined?
If we know Eion, we can predict the forces on ions at any membrane potential (very useful!)
* Walther Nernst (1864 – 1941) figured out how to calculate Eion
What does the Nernst Equation calculate?
Equilibrium potential for a particular ion
Nernst equation
Example of Nernst equation
Valence of different ions
Fun with the Nernst Equation!
What is the ionic driving force?
Energy pushing ions in or out of cell
Vm – Eion
What is ionic conductance?
Capability of an ion to cross the membrane
gion
Conductance vs. permeability
- Permeability is a relative measure comparing different ions
- High conductance or permeability means ions could cross the membrane
What is ionic current?
Conductance x driving force
gion(Vm – Eion)
Ion movement across membrane
Permeability, equilibrium, and Vm (Sodium Sammy and Potassium Penny)
If the cell membrane is permeable to only Na+, what will happen to Vm?
Vm will increase until it reaches ENa
If the cell membrane is permeable to only K+, what will happen to Vm?
Vm will decrease until it reaches Ek
Permeability to ions at rest
At rest, neurons are typically about 40x more permeable to K+ than Na+, so Vm at rest is much closer to Ek
Effects of aberrant resting potential (Weaver mice)
- Weaver mice” have a K+ channel mutation in the cerebellum that allows the channel to pass both K+ and Na+
- Because of increased Na+ permeability, resting potential is more positive than normal and neuron function is compromised
- Called “Weaver” because the mutation causes abnormal posture and movement (“weaving”). They also die prematurely (after death of motor neurons).
Axoplasmic transport moves various kinds of material along ___
Microtubules
The output elements of neurons are generally ___
Neurons
The formulation of neurofibrillary tangles in Alzheimer’s disease is triggered BY what factor?
Accumulation of beta-amyloid
Which ion is most concentrated inside the neuron compared to outside?
K+
The resting membrane potential of neurons is closest to the Eq for which ion?
Cl-
Describe the insulation of oligodendroglial cells
An oligodendroglial cell insulates portions of multiple axons
Which of the following occurs first in Alzheimer’s disease?
a) formation of amyloyd plaques
b) formation of neurofibrillary tangles
c) dissociation of microtubules
d) spread of infected tau
a) formation of amyloid plaques
The concentration gradients of K+ and Na+ across the neural membrane are established by
a) the sodium-potassium pump
b) the relative permeability of the membrane to each ion
c) the driving force on each ion
a) the sodium-potassium pump
