Neurophysiology (2) Flashcards
Where does the AP originate in response to the monosynaptic or myostatic stretch reflex?
In the peripheral process of a sensory neuron ( the cell body of which lies in the dorsal root ganglion)
What causes the stimulus for the AP fired in response to testing a tendon reflex response?
Stretch of muscle spindle fibers is transduced into a graded electrical signal, called a receptor potential
What nerve is the signal transferred to from the sensory neuron in the stretch reflex? Where in the spinal cord is this located
Alpha-motoneuron, located in the spinal cord ventral horn
Other than the alpha motoneuron, what nerve does the afferent sensory nerve synapse on in the spinal cord?
Interneuron. May inhibit firing of the motoneuron
What provides the stimulus for activation of a voltage-charged gate?
Charged amino acids
What are two mechanisms that can contribute to the selectivity pore of ion channels?
- Narrow pore (only certain molecules can pass; steric hindrance)
- Charged region in pore
What is Ohm’s Law?
Voltage = current X resistance. V= IR
How do resistance and conductance (G) relate?
Resistance = 1/ conductance
Which biological structures act as resistors in a neuron? How then is resistance controlled?
Ion channels. Act like variable resistors and resistance is controlled by channel gating.
What biological structure serve as a capacitator in neurons? What are the consequences of having capacitators?
Lipid bilayer. Electrical signals are slowed by the storage of charge in the membrane (capacitative element)
What is the time constant? What does it determine?
Time for membrane potential to fall to 1/e of original potential charge. Determines time period over which electrical signals can be integrated in a cell. Voltage is maximal at the point of stimulation and decays exponentially with distance from that point.
At rest, what ion are neuronal cell membranes permeable to?
Primarily K+
What does the Nernst equation determine?
The membrane potential at equilibrium if the membrane were only permeable to one ion.
What is the equilibrium potential in neurons for K+? Na+? Cl-?
K+ = -100 mV Na+ = +50 mV Cl- = -60 mV
What is the resting membrane potential for neurons typically?
-70 mV
What does the Goldman-Hodgkin-Katz equation predict?
The membrane potential at equilibrium when all permeant ions are taken into account
What two active pumps are responsible for maintaining the necessary ion concentration for the resting membrane potential?
- Na/K ATPase
2. Ca2+ ATPase
What does the complicated geometry of neurons mean for the membrane potential?
It is not the same at all points in the membrane (not isopotential) at a given time
Increasing what parameter will increase the time constant in electrotonic or passive signal propagation?
Increasing diameter of cable. Larger diameter means less contact with the membrane, so charge doesn’t leak as much
What causes the progressive decay in amplitude in passive (electrotonic) signal propagation?
Leakage of charge across membrane
There is also a slowing of response in passive signal propagation, what is responsible for this?
Charging of the membrane capacitance along the neuron
What type of signal is an active signal, that cannot be modeled by a simple RC circuit?
Firing of an AP
What is the undershoot, in which the membrane potential falls to less than the original called?
Afterhyperpolarization
What indicates that selectivity is maintained but but that a different ion species dominates membrane permeability during depolarization, compared to K+ at rest?
The fact that membrane potential overshoots 0 mV. (Goes up to + 30)
What are the two major types of neural electrical signals?
- Graded potentials
2. Action potentials
Graded potentials are ________ responses. Action potentials are ______ responses.
Passive; active
Why are action potentials/active responses voltage-dependent?
Because they rely on the opening of voltage-gated ion channels
What is responsible for the upstroke in an AP?
Increase in membrane permeability to Na+
What is responsible for the downstroke in an AP?
Inactivation of Na+ channels
What is responsible for the undershoot or afterhyperpolarization in an AP?
Increased potassium conductance due to voltage-gated K channels remaining open for a bit after the Na channels have been inactivated
For sodium channels, what is the difference between deactivated and inactivated?
Deactivation is the process of going from the open to the closed state, whereas inactivation means no ions can be conducted and no stimulus can activate them
What is required to “reset” an inactivated Na channel?
A finite amount of time at a negative membrane potential ( resting or less)
At resting membrane potential, what is the state of most Na channels?
Closed. As membrane becomes more depolarized, the probability of a Na channel being open increases, so by ~0 mV, almost all are activated
What feature of K channels, in contrast to Na channels allows them to facilitate attainment of threshold and to cause afterhyperpolarization?
They open more slowly, compared to. Na channels and therefore remain open for longer. They also don’t have an inactivated state ( at least not on time scales relevant for discussion of AP firing)
What is the relative refractory period? What channels are responsible?
Time after an AP during which a larger than normal stimulus would be required to fire a second AP. Is due to the K channels remaining open ( increased K permeability post-AP)
What is the absolute refractory period? What is responsible for this.
The period of time after an AP in which no stimulus can produce an AP. This is due to a high number of Na channels being in the inactivated state. If Na permeability cannot be increased, then the voltage threshold required for an AP cannot be achieved
Are Na channels considered positive are negative feedback? Why
Positive. The influx causes depolarization, which in turn opens more Na channels ( provided they aren’t inactivated, but only closed), cause more depolarization.
Are K channels considered negative or positive feedback in terms of depolarization? Why
Negative feedback. They allow positive charge to leak out of the cell, which depolarized the cell (brings it back closer to resting potential)
What is different about the amplitude of an AP signal over time compared to a graded potential? What accounts for the difference?
The amplitude remains the same in an AP, because the depolarization is regenerated in each patch of membrane ( the change membrane potential activates voltage-gated Na channels in each individual patch)
How do active and passive signal propagation mechanisms work together to conduct an AP stimulus?
APs are generated at one point (usually axon initial segment or at a node of Ranvier) then travel electrotonically (passively) to the next patch (next node, etc. where another AP can be generated aka a new signal with the same amplitude of the original signal)
T or F. Signals generated in the axon initial segment can propagate backwards into the soma and/or dendrites.
True. Signal propagation is only unidirectional in the axon itself
What two factors prevent backwards propagation of the signal within the axon?
- Inactivation of Na channels
2. Refractory period ( which is due to Na channels, also K channels)
Two ways to increase conduction velocity
- Increase axon diameter
2. Myelination
What two ways does myelin increase conduction velocity?
- Increases the resistance (prevent ionic leak)
- Decreases the capacitance ( less charge gets stored, or “stuck” to the membrane walls, so more is available to propagate)
Basically : facilitates the electrotonic (passive) propagation by preventing loss of charge
Other than myelination, etc why is decrement of the signal between nodes minimal?
Distance between nodes is short and AP current is usually very large
What two groups of neurons have the most rapid conductiong speeds?
- Alpha motoneurons
2. Group 1 afferents
In mammalian myelinated axons, what process is most important for repolarization?
Inactivation of Na channels ( more so than opening of K channels)
Why do APs iniate in Nodes of Ranvier or in the axon initial segment?
These areas have a high density of Na channels ( also some geometric factors)
Generalized epilepsy with febrile seizures is due to mutations in the Na channel subunit that alter their function how?
Mutations delay the inactivation of Na channels, leading to prolonged Na influx and thus hyperexcitability
The alpha subunit of the Na channel has ___ domains, each consisting of ___ transmembrane spanning regions
4; 6
Familial hemiplegic migraine is due to mutation in what type of channels?
P/Q-type Ca2+ channels ( CaV2.2 channels)
What is the channels patchy in Episodic ataxia type 2?
Truncated mutants of CaV2.2 channels
What is the pathology of Lambert-Eaton syndrome?
Antibodies to presynaptic voltage gated Ca channels are produced; often as part of a carcinoid syndrome in small cell carcinomas
What is myotonia? Mutations in which channel may cause these?
Hyperexcitability of muscle. Mutation on Cl channels can cause
Mutations in what channel underlie Episodic ataxia type 1? Where in the brain?
Kv1.1 type potassium channels, in Purkinje cells in the cerebellum
