Lecture 4 Flashcards
Na+ is smaller than K+ but has the same charge. How do K+ leak channels exclude Na+? (1) Experiment
Using x-ray crystallography, worked out the proteins shape and the shape of its pore
Figured that arginine was the protein with outlying carbonyl groups. Wanted to replace with lycine
Made the DNA with the sequence we wanted
Put into frog egg cell because it is large, easy to see and has few ion channels (so does not distort results).
Found a promoter region that works for all eukaryote cells and causes them to express the protein.
Put it into frog and soon the frog was covered in modified channel
Thus found what group prevented NA= from crossing
X-ray chrytsalography
Get a pure protein sample
Crystallize it
Image with xrays and detect their diffusion pattern
Allows the derivation of the only shape the protein could have
Na+ is smaller than K+ but has the same charge. How do K+ leak channels exclude Na+? (2) results
Ions in water get coated in water
Carbonyl groups in channel are optimally speced to interact with the K+ group and so decoat it so it travels through the pore alone.
Na+ is smaller and so cannot optimally interact with the pore hence, is not decoated (and thus cannot fit)
the 40 kinds of voltage gated potassium channels
what is there genetic origin
have they been conserved
what influenced a choice for them
First appeared before multicellular organisms
Has been conserved for hundreds of millions of years
No perfect one, cell chooses which to express to optimize cell functions
Weird use of modern neuroscience
speed up activation
Lidocane is slow, can try to speed up by using electrical communication
Make an ion channel that opens in response to light. Brain is normally dark so none evolved but certain species of algea have these.
Take these and modify them if needed
An example is making mice aggressive by making their amygdala activate via lasers
Neuroglia
more glia or neurones
Glial cells are all over the neurons. Help traffic neurons and maintain molecular stability in the extracellular space. The outnumber neurons by between 2:1 and 5:1
Support cells: astrocytes
physical support and cleans up debris via phagocytocis. Control chemical composition of the surrounding area to nourish neurons
Support cells: microglia
Smallest glial cells
immune function
CNS does not allow most immune cells in so has its own
Support cells: Oligodendricytes
Make the myelin sheath
During development make processes like canoe paddles
Each wraps itself around a neuron many times and thus produces layers of mellin that make the myelin sheath
Myelin sheath
Insulation
Made of fat
Speeds up conduction in the neuron
each wrap is about 20 microns long and their are gaps in between that are 1 micron long
The distribution of ions and the mechanism of saltatory conduction
Charged ions aggregate at the membrane. Negative ones in it and positive ones outside it. Further from the membrane, there is less aggregation because there is no electrostatic force making it so
at a node of ranvier, when an action potential happens, positive ions (Na+) come in and immediately stick to the membrane as discussed. These new positive ions repel the old positive ions that were in solution in the cell. These move further away in both directions.
The next node becomes depolarized. The last node is still in the refractory period and blocked by the balls and chains of the Na+ voltage gated channels. So the action potential is only propagated in one direction
As the movement of ions goes away from the node, it is decremental. It is regenerated at the next node
This makes conduction 20x faster
Things that speed up action potentials
Size of axon (less resistence)
Mylenation
Example of different mylenated and not conduction speeds
Touch something hot
The touch is mylenated so can feel you have touched. Pain and temp is not so it takes a second before that info makes it to your brain
Synapses very basics
Junction between axon terminal of sending neuron and the receiving neuron
Communication goes from the axon terminal to the membrane of the other cell
This communication is mediated by a neurotransmitter
The synapse structure
The terminal bouton contains synaptic vesicles
When the action potential arises it opens voltage gated ca2+ channels which allow Ca2+ in. This binds immediately to receptors which trigger the exoxcytosis of the contents of the synaptic vesicles
This free neurotransmitter diffuses across the synaptic cleft and binds to recpetors on the post synaptic membrane
Size of things in synapse
mitochondria is 1um
Omega shapes
Are formed by synaptic vesicles undergoing exocytosis and releasing their neurotransmitter
Ligands
Generic name for signaling molecule that binds to the binding site of a receptor
Neurotransmitters are ligands
Binding site
:ocation on a receptor to which a ligand binds
Postysnaptic receptor
Receptor protein on postsynaptic membrane that neurotransmitter binds to
Ligand-gated ion channel
A receptor that is an ion channel. Also known as an ionotrophic receptor. Opens when a ligand binds to it
2 categories of neurotransmitter receptors
Ionotrophic - is an ion channel
Metabotropic - are a g protein coupled receptor that can open ion channels through an intracellular signaling cascade
intra cellular, Post, pre and extrasynaptic receptors
Post are post
Pre is pre
Intracellular receptors are stored receptors waiting to be used
Extrasynaptic receptors are stored receptors waiting to be used (on membrane, not at synapse
When cell needs new receptors, it uses the extrasynaptic ones andmoves intracellular ones to the membrane in their place
Ionotrophic receptor mechanism
Ion binds
Receptor no longer stable in this form
Changes form which allows ions to move through
New form not stable with ion that is bound to receptor
Breaks off and leaves
Now channel no longer stable in this shape, turns back
No more ions can pass
takes half a milisecond
Termination of postsynaptic potentials
Enzymatic deactivation - enzyme breaks up neurotransmitter
Reuptake - Reentry of a neurotransmitter just liberated by s terminal back through its membrane for recycling or the same but with the products of neurotransmitter breakdown
Postsynaptic potentials can be (2 things)
Excitatory or inhibitory
Excitatory post synaptic potential (EPSP) or current (EPSC)
Na+ in
Makes more positive
Inhibitory post synaptic potential (IPSP) or current (IPSC)
Cl- in
Makes more negative
Neural Integration
One EPSP is not enough to casue an action potential. The depolarazing effect will be balanced by K+ leaving the cell. Many EPSPs have to happen at once.
Na+ has to come in faster than K+ can leave and this =ve charge must reach the axon hillock where the new action potential will be made
When EPSPs and IPSPs come in at the same time the Cl- ions decrease the chance the cell will fire.
Hence, the activation is a balance between the two
What determines if a neurotransmitter is inhibitory or exititatory
The receptor
The same neurotransmitter can activate many receptors. The cell chooses the one it wants to express. Some let in Cl- (inhibitory) some Na+ exitation
Relfex
Painful stimulus
Sensory neuron activated
Goes to CNS, activates interneuron
This activates motor neuron
This activates muscle
Top down moderation of neurons
There are many cells from the brain that act on interneurons. Some inhibit them, some excite them.
Brain can moderate interneuron and hence some reflexes
Inhibitory networks
Inhibitory neurons reliably cause IPSPs downstream
But sometimes these act on inhibitory neurons and hence can make a behaviour more likley to occur
Often big chains
Neural excitation is not the same as behavioural excitation. Neural inhibition is not the same as behavioural inhibition.
