Lecture 1, Chapter 1 Overview: History and the neuron
History
Galen
Nerves were tubes, brain had holes (ventricles)
______flowed through the tubes, much like ______
Ramon y Cajal
Showed that nerve cells were ______and not networks of tubes
Noticed ______between units
Noticed ______(cell bodies)
How does one part of the body communicate with another part?
Loewi (1921)
Stimulated the vagus nerve in one heart to ______it down
Removed some of the fluid it was bathed in
Added that removed fluid to a different heart
The second heart ______
Some ______must be working to slow the heart
What is the nature of these chemicals?
Hodgkin and Katz (1949)
Working with giant squids can lead to problems
“The values for spike height are in good agreement with those obtained by Hodgkin and Huxley (1945), but are considerably smaller than those reported by Curtis and Cole (1942). The average value for the resting potential is slightly smaller than that given by Curtis and Cole… The average action potential was about 20mV smaller than that given by Curtis and Cole. But a more serious discrepancy arises from the fact that we have never observed action potentials greater than 100mV at 18-23 degrees C, whereas Curtis and Cole describe a spike as large as 168mV in a fibre which gave a resting potential of 58mV. The matter is not one that can be lightly dismissed, because the existence of a fibre capable of giving an overshoot of 110mV has far reaching implications. We can no longer be inclined to think that our relatively small action potentials can be attributed to the poor condition of the experimental animals, since a number of the squids employed were extremely lively and in perfect condition. Nor does it seem likely that axons were damaged in the process of isolation… the only explanation that can be offered is that there is a real difference between the properties of L.Peali used at Woods Hold and L forbesi used at Plymouth.”
What did they find?
Knew that when frog muscles are put into a solution with low levels of sodium and chloride, they were ______
So either sodium or chloride in needed for excitation
Replaced chloride in sea water solution with sulphate and the nerve was ______
Conclusion: ______is at the root of the action potential
What about increasing sodium levels?
“The concentration of sodium chloride was increased… This solution…damaged the axon by osmotic effects in 5-15 min. But before the osmotic effects became apparent the axon gave an increased action potential with characteristics which were the converse of those in sodium-deficient solutions.”
The Resting Potential
A difference between the voltage of the inside and the outside of the neuron (approx -70mV)
Occurs because ions are found in different amounts inside of the cell compared to outside of the cell
The players:
______(Na+)
______(K+)
______(Cl-)
Other Anions (A-)
Two forces at work in a neuron
Electrostatic gradient
Charge- ______
Diffusion gradient
______
Why don’t ions just move to where the forces push them?
______membranes
Contain ion channels which open and close to let certain ions in or out of the cell
Two types of channels
______channels
Opened by a chemical
______channels
Opened by a change in voltage
The sodium potassium pump
Forces three sodium ions out of the cell for every two potassium ions brought back in
Creates an ______between the inside and the outside
The outside gets more sodium, which makes it more ______
Takes up to 20% of a cell’s energy to keep going
In addition
Ion channels are “______”
Small amounts of ions get through even when the channels are “closed”
This further contributes to the status of the resting potential
______by the sodium potassium pump
The action potential
Ligand gated channels play a large role
Opened by a ______
The chemical is usually a neurotransmitter
Some chemicals ______the amount of positive ions entering the cell
Others increase the amount of ______ions entering the cell
EPSPs and IPSPs
If the inside of the cell becomes more positive, this is called an ______(EPSP)
If the inside of the cell becomes more negative, this is called an ______(IPSP)
Keys to the action potential
If enough of an EPSP leads to the surpassing of the threshold (approx -55mV), an ______
The increase in voltage inside the cell triggers the opening of more and more ______sodium channels
These allow a LOT of sodium to enter the neuron and increase the positive charge inside the cell
Keys to the action potential
Around +40 to +50mV, the sodium channels ______, leaving just the potassium channels ______
Potassium is now repelled to exit the neuron by the positive charge inside (electrostatic force) and by its concentration gradient
Too much potassium leaves and the cell becomes ______
Refractory period
While the cell is hyperpolarizing, it cannot fire again (sodium channels are unable to open)
______refractory period
Once the potassium has overshot the resting potential (too much left), the cell can re-fire if it receives a larger than average EPSP
______refractory period
Getting back to rest
Due to the sodium potassium pump, the resting potential is eventually ______and the cell is ready to go again
“leaky” channels aid in this process as well
The axon terminal
The change in voltage in the axon terminal leads to the opening of voltage gated ______channels
______Calcium leads to ______- the neurotransmitter is released into the synapse
The synapse
The neurotransmitter crosses the synaptic gap and ______on the postsynaptic neuron
Many different types of receptors exist
Action of NTs at synapse
Receptors can be either single step or multiple steps
______: single step
NT binds to channels and opens them
Can work quickly: ______
______receptors
Multiple steps
NT binds to receptor- triggers G protein to bind to ion channel and open it
The majority of receptors in the brain are metabotropic
Slower than ionotropic receptors: ______