L3 - Graded Potentials and APs (Chapter 5) Flashcards
What was the basic idea of Galvani’s experiment?
Galvani did experiment where he hooked a frog up to a lightning rod, and when lightning would strike, the frog would move (muscles were contracting)
Who were Luigi Galvani and Alessandro Volta?
- Galvani had a rivalry with Volta (invented the battery to create a set of data in order to compete with Galvani) as to whether or not animals had an innate ability to intrinsically produce electrical activity (animal electricity)
- Galvani was proved correct
Who was involved in the discovery of APs in 1865?
- Emil du Bois-Reymond developed the galvanometer
- Julius Bernstein developed the differential rheotome
Who was involved in the first intracellular recording in 1939?
- Alan Hodgkin and Andrew Huxley
Who was involved in the first voltage clamp recording in 1947?
Kenneth Cole and George Mormont
Who was involved in the discovery of the ionic basis of APs in 1949?
Alan Hodgkin and Bernard Katz
Who was involved in the first patch clamp recording in the 1970s?
Erwin Neher and Bert Sakmann
Depolarization
- membrane potential becomes less negative/more positive
- excitatory effect
- 1st arrow in picture
Repolarization
- membrane potential becomes more negative/less positive
- 2nd arrow in picture
Hyperpolarization
- membrane potential goes more negative than resting membrane potential
- inhibitory effect
- 3rd arrow in picture
What are graded potentials?
- variable/graded in amplitude
- amplitude is proportional to the amplitude of the stimulus
How are APs different from graded potentials?
APs are all or none, and once threshold is reached, the same amplitude will be generated every time
How do AP’s and GP’s propagate differently?
- APs are unidirectional, and propagate away from the soma because the membrane behind the AP enters a refractory period
- Graded are bidirectional, depolarization occurs in both directions
Which type is regenerative (AP or graded)? Which type is decremental? What do these terms mean?
- Graded are decremental, meaning that the voltage change does not get regenerated and continues to diminish
- APs are regenerative, there is a mechanism that actively regenerates the voltage change through positive feedback
Which can summate and which cannot (APs or graded)? Why or why not?
- Graded summate - have a slower response than APs, which allows for the amplitude to be summated, creating an AP
- APs do not summate because they follow the all or none principle - meaning that they must reach a specific voltage in order to be generated
Where can AP’s be generated vs GP’s? What determines the parts of the cell where AP’s are generated?
- APs are generated in the axon/axon hillock - require specific membrane proteins in order to be propagated across long distances
- Graded are generated in the soma or dendrite
What name does your Guyton and Hall textbook use to refer to graded potentials? What does this name mean? What properties does it refer to?
- acute local potential
- short lived and short distance
What is the time constant?
- The time it takes for the membrane potential to change by 63% of the total change
- How much time it takes the membrane to change/depolarize based on the stimulus
- measured in seconds or milliseconds
How is the time constant calculated? Can you draw this graph?
= to membrane resistance x membrane capacitance (T = Rm x Cm)
What biophysical properties of cells affects their time constant?
- Membrane capacitance and membrane resistance
- Rm can be altered by number of channels and whether or not they are open – more channels = less resistance
- Cm can be altered by the thickness of the membrane (depends on myelination) - increased myelination will decrease capacitance
How can the time constant affect signaling in excitable cells?
- the larger the time constant of a cell, the longer it takes to respond to a stimulus
In the picture, which cell has the larger time constant? Cell A or B?
- A has the larger time constant bc it’s taking longer to reach max potential
- B has the smaller time constant bc it has more channels, meaning that the membrane resistance is smaller than that of A
What is the length/space constant?
- How far the potential will travel before the amplitude of the membrane diminishes to 37% of the maximum value
- Measured in units of distance (meters or millimeters), and is indicated by lambda
How is the length constant calculated? Can you draw this graph?
= Square root of membrane resistance/axial resistance
What biophysical properties of cells affects their length constant?
- Rm and Ra
- Rm is altered by number of ions channels - would need to increase in order for signal to go further
- Ra is altered by the size of the membrane - would need to decrease in order for the signal to go further
Spatial summation
- summation over space, the combination of amplitudes to create a larger one
- in the picture, spatial summation is shown by 1+3 and 2+3
Do graded potentials or APs participate in spatial summation?
graded potentials
What is a receptor potential?
type of graded potential that is generated by activation of sensory receptors
What are some different types of sensory receptors we discussed?
- mechanoreceptors transduce mechanical force into electrical changes (mechanically gated ion channels open, allowing for APs to be created)
- thermoreceptors, chemoreceptors, baroreceptors, photoreceptors
What is a PSP?
- post synaptic potential, the potential that occurs in the postsynaptic cell, receptors that respond to neurotransmitters create a voltage change, which is a PSP
- EPSPs – excitatory, depolarization
- IPSPs – inhibitory, hyperpolarization
- type of graded potential
What is an EPP?
- end plate potential, only found in skeletal muscle in the NM junctions
- large, have ligand gated ion channels (ACh binds to these) that create PSPs
- type of graded potential
What is AP threshold? What is the typical value of threshold?
- high enough depolarization that allows the cell to create an action potential
- 10-20mV depolarization from resting membrane potential
What is the mechanism of threshold?
- All or nothing response is a positive feedback loop – carries the cell away from homeostasis quickly
Who is credited with discovery of the action potential?
Emil du Bois-Reymond
Be able to draw/label/identify graphs displaying changes in conductance or current that occurs during each phase of the AP.
Did Hodgkin and Katz demonstrate a dose-dependent effect of diminishing [Na+]e? Why is this important?
- Yes, when extracellular Na was reduced, the amplitudes of the AP got smaller
- cannot do this with K bc you’ll be interrupting the cell’s membrane, which will make the cell sick and alter results
How were Hodgkin and Katz able to rescue the AP after abolishing it?
- By adding choline
- By adding sodium back into the seawater/extracellular Na
- Did this in order to prove that the effects of diminished Na were reversible, and that they weren’t killing the cells
Be able to compare and contrast v-gated Na+ and K+ channels.
- K channels
- do not have an inactivation mechanism
- have a lower activation rate
- activation occurs at peak of AP
- Na channels
- more complex than K channels
- have two gates
- faster activation, slow inactivation
How does the kinetics of activation/inactivation compare between Na+ and K+ channels?
- Na channels are fast channels, but do have a slow inactivation
- K channels are slow channels
What are some ways in which AP waveforms can be changed?
- Phosphorylation of channels, or binding of hormones or NTs
- Extracellular concentration of ions can also alter channel gating
What are some potential consequences for changing AP shape?
Absolute refractory period
- period in which no matter how much stimulus is given, absolutely no AP can be generated
- excitability is nil, and threshold can be equated to infinity
Relative refractory period
- period of time following generation of an AP where the cell membrane becomes insensitive to further stimulation
- requires a larger stimulus to create another AP
Which is longer? Relative or absolute refractory period?
relative refractory periods are longer
What is the mechanism of relative refractory periods?
- due to leakiness of membrane to potassium
- once K channels are repolarized or hyperpolarized back to resting membrane potential, Na channels are reset, in which an AP can be generated
What is the mechanism of absolute refractory periods?
- due to the inactivation of Na channels
AP firing frequency
the rate at which APs are being generated
What determines the maximum AP firing frequency?
absolute refractory periods
What are the two different patterns of AP generation?
- tonic firing pattern - cell will continue to fire APs at a specific frequency in response to a prolonged stimulus (neurons in brain stem that are responsible for breathing)
- phasic firing pattern - cell will fire a burst or one AP in response to a prolonged stimulus (learning and memory)
What is the mechanism of phasic AP generation?
accommodation - in response to a prolonged stimulus, the cell may fire a single or a burst of action potentials, and then become insensitive to more stimulation
Why is the ability for some excitable cells to adapt physiologically (accommodation) important?
- some sensory receptors only need to measure change, and some need to have the ability to measure constantly
- the receptors that only need to measure change will have the accommodation response (EX: recording the change in body position)
How can changing the intensity of a stimulus affect the frequency of AP’s in excitable cells?
- once the AP fires, the cell is in its relative refractory period, and depending on the intensity of the stimulus, threshold will be reached faster or slower
- higher intensity stimuli = threshold reached more quickly
- lower intensity stimuli = threshold reached more slowly
Why is AP propagation said to be a regenerative process?
positive feedback loop due to Hodgkin Cycle
Hodgkin Cycle
- Stimuli
- membrane is depolarized
- opening of voltage gated Na channels
- influx of Na further depolarizes membrane
- membrane is depolarized to threshold, creating an AP
Continuous conduction
- propagation of APs in unmyelinated axons
- slower AP velocity
Saltatory conduction
- propagation of APs in myelinated axons
- faster AP velocity
- requires more energy
- EX: quick reaction needed when you touch a hot stove
Nodes of Ranvier
- gaps in myelin sheath that regenerate APs
- without these, APs wouldn’t be able to be propagated
- voltage gated sodium channels are here
Internodes
myelinated regions of the axon
Why don’t AP’s back-propagate once they begin to propagate in a given direction?
- if in the SIZ - there are no Na channels in the cell body present to allow it
- if further down the axon - the membrane behind the AP is in its refractory period
In neurons, why do AP’s propagate away from the cell body toward the axon terminal?
- because they are initiated in the Spike Initiation Zone, which is located at the axon hillock
- there are no Na channels behind the axon hillock (in the cell body) that allow the AP to propagate backwards
Experimentally, how can one cause AP’s to propagate in the opposite direction?
- stimulation at a more distal site on the axon
- like lighting a fuse in the middle
What is the difference between antidromic and orthodromic propagation?
- orthodromic - propagation of the AP in a single direction from the cell body to the axon terminal
- antidromic - propagation of the AP towards the cell body AND towards the axon terminal
How can conduction velocity be measured and calculated experimentally?
- via a stimulator and recording electrode
- measure the distance btwn the two, and measuring the time it takes for the stimulus to reach the recording electrode
- distance/time
How does myelin affect Rm? Cm? Ra?
- increases Rm and Ra
- decreases Cm (capacitors need a thin membrane to function well)
How does Rm and Cm differ at internodal regions?
- both are lower at internodal regions
- signals travel faster because of this
How does myelin affect conduction velocity?
- increased myelin decreases Cm and increases Rm
- decreases passive (electrotonic) conduction, and will increase the length constant
How axon diameter affect conduction velocity?
- the larger the diameter, the smaller the resistance (Ra), allowing for faster propagation & vice versa
- increases passive (electrotonic) conduction, and will decrease the length constant
What are the mechanisms for how each adaptation affects CV?
How does the length constant affect CV and node spacing in myelinated axons?
- the larger the length constant, the further the depolarization spreads, the faster the AP is propagated = faster CV
- larger jumps btwn internodal areas = faster CV
How does myelin affect the length constant?
increases it
