NPB101 MT1

Cell Physiology, Systematic Physiology, Nervous System

Can the cytosol produce ATP?

Yes, glycolysis will yield 2 ATP

Where are leak channels and what is their role?

• Na+ and K+ leak channels are ubiquitously distributed on the PM

• They are always open to allow free passive diffusion that maintains RMP

What are the trigger zones of an axon and what type of channel do they control?

• Axon hillock, Nodes-of-Ranvier

• Voltage-gated channels

How many states do K+ and Na+ channels exist in?

• K+ channels have 2 (activated or deactivated)

• Na+ channels have 3 (activated, inactivated, or deactivated)

What is the difference between inactivated and deactivated?

• Inactivated: pore is blocked and cannot be opened by depolarization unless the inactivation ball-and-chain is first removed by hyperpolarization

• Deactivated: gate is closed, but can be opened by depolarization

Why is the undershoot necessary?

Hyperpolarization removed the inactivation ball-and-chain

What channel controls the rising phase of AP?

Voltage-gated Na+ channels activate in response to threshold depolarization and Na+ influx causes the rise.

What channel controls the falling phase of AP?

Voltage-gated K+ channels activate delayed to threshold depolarization and K+ influx causes the fall and hyperpolarization. This is why VG K+ channels are called “delayed rectifiers”. Additionally, there is a very strong driving force into the cell because +30mV is very far from E(K+)=-90, therefore the falling phase is very rapid and includes an undershoot.

What does depolarization to threshold (-50mV) do?

Activate VG Na+ and K+ channels (although K+ channel response is delayed)

Does the concentration gradient of K+ or Na+ ever switch directions during action potential?

No, they change in magnitude but not direction since action potential doesn’t reach or pass either ions equilibrium potential (-90mV or +60mV).

How is the voltage-gated Ca2+ channel opened and what is its role?

• Opened by AP depolarization reaching the presynaptic axon terminal’s membrane

• Ca2+ initiates the migration of NT vesicles and completes vesicle-PM fusion that results in exocytosis (In other words, Ca2+ mitigates NT exocytosis)

What is the ligand and selectivity of the AMPA receptor?

• AMPA ligand is glutamate

• AMPA selective for BOTH NA+ and K+

What is the role of the AMPA receptor?

To generate an EPSP (excitatory)

What is the ligand and selectivity of the nAchR?

• nAchR ligand is Ach

• nAchR is selective for cations (+)

What is the role of the GABA receptor?

To generate an IPSP (inhibitory)

Where are nAchR located and do they result in a EPSP or IPSP?

• NMJ and ANS ganglionic junction

• EPSP

Are nicotinic receptors ionotropic or metabotropic?

Ionotropic

What kind of channel is a cGMP channel?

Ligand-gated channel opens in response to cGMP binding and selective for cations (NA+)

What cell type and system are cGMP ch part of?

• Photoreceptors

• Visual

How is light perceived or not? Condition: Dark

In the dark, rhodopsin remains inactive. Thus, cGMP levels are high and ion channels are open. Na+ influx allows depolarization to -40mV that opens VG Ca2+ channels. This process results in the exocytosis of inhibitory NTs that inhibit the perception of light.

Dark → inhibitoy NT release —/ light perception

How is light perceived or not? Condition: Light

Light hits rhodopsin which separates into an active retinal and bleached opsin. The bleaching of opsin activates a neighboring transducin which activates a G-protein cascade resulting in the expression of cGMP phosphodiesterase. The enzymes activity decreases the concentration of cGMP (light = low cGMP). Therefore, LG Na+ channels close and K+ leak channels rectify Vm. This means VG Ca2+ channels can’t open and the inhibitory NT is not released. This process is essentially inhibition of inhibition of the perception of light.

Light → cGMP phosphodiesterase —/ cGMP —/ depolarization → inhibitoy NT release —/ light perception

Light → light perception

What class of channel are stereocillia and Pacinian corpuscule?

Mechanically-gated channel

What is the goal of negative feedback?

To oppose a deviation from set point caused by a stimuli

What are the elements of a negative feedback loop and what are their fuctions?

• Sensor: detects stimuli

• Integrator: compares the value from the sensor to the set point

• Effector: If there is a significant change, the effector causes a response to adjust the controlled value back to set point

What are the two forms of homeostatic control?

Intrinsic and extrinsic

Intrinsic homeostatic control:

local changes of a system built into the organ

Extrinsic homeostatic control:

response system outside of the organ that results in combinatorial control over several organs

Are set points fixed?

No, they are dynamic according to the bodies needs and operate within a narrow range

Does the cellular response depend on the identity of the ligand or the receptor?

cellular response depends on the identity of the receptor

What are the four receptor types?

• nuclear receptors - intracellulary located to control gene expression

• GPCR - metabotropic receptors that use a secondary messenger

• Ionotropic receptors - act as ion channels

• enzyme-linked receptors

What processes do carriers perform?

(i) Facilitated diffusion - fixed affinity binding site transports down gradient

(ii) Active transport (via. pumps) - binding sites of variable affinity transport up the gradient

What does the ATPase pump transport?

• 3x Na+ out

• 2x K+ in

How do the pumps binding affinity relate to concentration?

There is an inverse relationship

• high [ion] = low affinity for ion

• low [ion] = high affinity for ion

Does charge separation effect the bulk solution of ions?

No, the amount of ions involved in charge separation is insubstantial compared to the amount in bulk solution. Meaning the inside of the cell will always be negative (determined by NAs) and the outside will always be more positive.

The electrical gradient is caused by what?

Electrostatic interactions at a distance (“field effects”)

When calculating net driving forces what value is used for the chemical and electrical driving forces?

• Electrical driving force = Vm

• Chemical driving force = E(ion)

Where is [K+] high?

inside the cell (banana of the banana in the sea metaphor)

Where is [Na+] high?

outside the cell (sea of the banana in the sea metaphor)

Define resting, equilibrium, and reversal potental

• Resting potential (of membrane) = no net flow of any ions across the PM

• Equilibrium potential (of ion) = no net flow of a specific ion

• Reversal potential (of channel) = no net flow of any ions through a specific channel

Are cells more permeable to K+ or Na+ at RMP?

30-fold for K+ because the PM has more K+ channels

What are characteristics of graded potential?

• generated by a transient injection of current

• Decrease in size as it flows further from its source

What is the brain?

a synaptic network!

What marks the absolute refractory period?

• time between the activation of Na+ channels to the inactivation of Na+ channels

• Another AP spike can NOT be generated under any circumstances

What marks the relative refractory period?

• time between the inactivation of Na+ channels and the deactivation of Na+ channels

• The depolarization event required to initiate another AP spike must be greater than at rest

What is the status of each channel at each state of AP?

• RMP - Na+ channels deactivated, K+ channels deactivated

• Rising phase - Na+ channels activated, K+ channels deactivated

• Peak of AP - Na+ channels inactivated, K+ channels activated

• Falling phase - Na+ channels inactivated, K+ channels activated

• Hyper polarization - Na+ channels deactivated, K+ channels activated

• Return to rest - Na+ channels deactivated, K+ channels deactivated

Order of channel activity during AP spike …

Na+ channels activated → Na+ channels inactivated/K+ channels activated → Na+ channels deactivated → K+ channels deactivated

What typed of channels does AP depend on?

Voltage-gated Na+ and K+ channels

What is necessary for grades potentials to cause an AP?

temporal AND spatial summation

What is continuous conduction?

• Uninterrupted flow of AP through an axon

• Only possible in axons with large diameter because Ri<Rm therefore the favorable path is through the axon rather than leaking out leak channels

• Channels are evenly dispersed

What is saltatory conduction?

• AP jumps between nodes

• Myelin increase Rm solving the problem of Ri>Rm in narrow neurons

• Channels are concentrated at the nodes

• Allows fast and reliable long-distance transduction

What ensures unidirectional AP propagation unlike in graded potentials?

Inactivated Na+ channels - also would annihilate experimental APs from opposite direction

Multiple Sclerosis

• Autoimmune disease attacking myelin in the cerebellum

• Slow and unreliable movements

• Action tremors - tremors during voluntary movement

Parkinson’s

• Disease affecting the Basal ganglia

• Resting tremors - tremors when movement is not being voluntarily initiated

What is the role of the cerebellum?

To compare actual movement with intended movement and make adjustment is necessary

What is the role of the Basal ganglia?

planning and initiation of movement

What is the role of the Wernick’s area?

language comprehension

What is the role of the Broca’s area?

speech production

What would differ in patients affected by damage to the Broca’s area and Wernick’s area?

The patient with damage to their Broca’s would be able to respond but not talk (response would be nonverbal) vs the patient with damage to their Wernick’s would be able to talk but not respond (irrelevant babbling)

Chemical synapses

direct electrical coupling between a presynaptic neuron and a postsynaptic neuron or effector muscle/gland

What ion is NT release directly dependent upon?

Ca2+

Can NT receptors be either ionotropic or metabotropic?

Yes, an ionotropic example is nAchR and a metabotropic example is the mAchR in the parasympathetic ANS.

What is the order of events in neuronal signalling?

1. Summation of graded potentials trigger axon hillock

2. Na+ channels activated causing depolarization

3. Depolarization travels down axon to open VG Ca2+ channels

4. Ca2+ causes endocytosis of NT

5. NT diffuse in the synaptic cleft

6. NT bind to receptors on the postsynaptic membrane causing cation flow into postsynaptic cell

7. EPSP or IPSP can be triggered in postsynaptic cell 

How are NTs cleared from the synaptic cleft?

1. Diffusion causes dilution

2. Degradation by extracellular enzymes 

3. Re-uptake (eg. serotonin, dopamine)

What are the major differences between the NMJ and a neuronal synapse?

• Acetylcholinesterase is present to rapidly degrade the signal allowing for precise skeletal muscle control

• ESPS are typically large enough to cause AP

Are ionotropic or matabotropic receptors fast/slow acting?

• Ionotropic = fast

• Metabotropic = slow

Myasthenia Gravis

• Autoimmune disease of NMJ attacking nAchR

• Cases muscle weakness during sustained activity (commonly eyes, face, swallowing)

How is Myasthenia Gravis treated?

With neostigmine which inhibits acetylcholineesterase to prolong Ach signal

What ion is dominant through AMPA receptor at RMP?

Na+ because it has a greater net driving force since E(Na+)= +60mV is further from RMP= -70 mV than E(K+) = -90mV

What is the reversal potential of AMPA?

0mV (greater than threshold because excitatory)

If the reversal potential is greater than threshold is the receptor excitatory or inhibitory?

excitatory 

If the reversal potential is less than threshold is the receptor excitatory or inhibitory?

inhibitory

Afferent neuron is in which spinal chord root?

Dorsal root (At the Door)

Efferent neuron is in which spinal chord root?

Ventral root (Exits the Vent)

What are the four branches of synapses required of the afferent neuron in a withdrawal reflex?

1. Excite the efferent neuron connected to the flexor (flex the flexor)

2. Inhibit the efferent neuron connected to the extensor (slacken the extensor)

3. Communicate with the other leg (opposite effects)

   • Inhibit the efferent neuron connected to the flexor (slacken the flexor)

   • Excite the efferent neuron connected to the extensor (flex the extensor)

4. Send a signal to the brain

   • Sequentially last because you react before you feel pain

What is the reason for cortical magnification?

Behavioral significance

What is the pathway of sensory transduction?

Receptor cell → relay nuclei → thalamus → primary cerebral cortex → higher cerebral cortex

What do receptor cells do?

Specialized to transduce stimuli energy of a specific modality (eg. light, touch, sound) into a change in membrane potential

What do receptor potentials do?

Generate AP that carry info about the rate and timing of the stimuli

What factors does acuity depend on?

• Receptor density on sensory epithelium

• Size of receptive field

• Lateral inhibition

Does a broader or narrower receptive field contribute to better accuity?

narrower receptive field = better acuity

What does lateral inhibition do?

Narrows the receptive field to increase acuity

When discussing a receptive field, how many neurons are being considered?

The receptive field refers to the range of location on a sensory epithelium that stimulates a single neuron

Rods vs cones

• Rods are for low light levels and do not distinguish wavelengths (night vision)

• Cones are for bright light levels and distinguish between wavelengths (color vision)

What is the optic chiasm?

The point at which incoming visual info from the optic nerve is split into optic tracts

Is each side of the visual field destined for the same or opposite hemisphere of the brain?

Opposite

Do optic nerves carry visual info from the same eye or side the the visual field?

Same eye

Do optic tracts carry visual info from the same eye or side the the visual field?

same side of the visual field (and they are in the opposite side of the brain than the side of the visual field)

What is the flow of sound through the auditory system?

reflect of the pinna → ear canal → vibrate the tympanic membrane → efficient ossicles mechanically activated by the vibration → oval window → fluid movement in the cochlea

How is the cochlea organized

• stiff and narrow for high pitch

• compliant and broad for low pitch

How does vibration activate the mechanically-gated stereocillia ion channels?

Up and down movement of the basilar membrane (caused by fluid movement) in juxtaposition with the stationary tectorial membrane bends the hairs opening their channels

Do sounds of vibrate the entire length of the cochlea?

No, only the part corresponding to the frequency/tone of the sound

What are the characteristics of phasic signaling?

• encapsulated receptors

• fast adaptation to sustained stimulus

  • Allowed by diffusion of signal from stretching of layers

• brief on and off response

What are the characteristics of tonic signaling?

• non-encapsulated receptors

• sustained response

Where is voluntary movement initiated?

Motor cortex

How many times do descending pathways cross the midline?

Exactly once!

Loss of function testing

• examine brain of deceased patient who suffered behavioral deficit to triangulate damage from trauma, stoke, etc to specific region in brain

Is the brain functionally organized?

Yes!

Passive observation

• Observe brain during instructed activity

• fMRI better spatially

• EEG better temporally

Perturbation/Intervention

Use electrodes to test artificial stimulation of a particular area of the brain and observe the resulting response

What was the behavioral deficit of Patient HM who suffered damage to his hippocampus?

• Total anterograde amnesia after removal of hippocampus

• Partial retrograde amnesia until original accident