SI Sunday October 18, 2009

Action Potentials and Synaptic Transmission

Action Potentials:

Label the following on the image below

1

SI Sunday October 18, 2009

Action Potentials and Synaptic Transmission

Graded EPSPs

Threshold Value

VGNaC Activation Gate Opens

VGNaC Activation Gate Closes

VGNaC Inactivation Gate Closes

VGNaC Inactivation Gate Opens

VGKC Opens

VGKC Closes

Absolute Refractory Period Begins (and why)

Absolute Refractory Period Ends (and why)

Relative Refractory Period Begins

Relative Refractory Period Ends

Rising Phase / Depolarization

Falling Phase / Repolarization

Undershoot and Overshoot

1

SI Sunday October 18, 2009

Action Potentials and Synaptic Transmission

(SEE THE DOCUMENT TITLED “COMPONENTS OF AN ACTION POTENTIAL” IN THE EXAM 3 FOLDER)

1. As you move from the dendrites towards the axon, at what anatomical region in the neuron do you start to find large concentrations of voltage-gated sodium and voltage gated potassium channels? What is the significance of this?

Voltage gated sodium channels. The significance is that graded depolarizations must spread passively and sufficiently to achieve threshold in this region in order to initiate an action potential. Once that has been accomplished, the voltage gated channels all along the axon will take care of the rest of the work (ALL-OR-NONE). SO, this is the region where “decision making” gets converted to an “irreversible action”.

2. Define absolute and relative refractory periods. When do they start and end and what are the corresponding events occurring within certain ion channels?

The absolute refractory period is the period in which it is impossible to generate another action potential. It starts when the action potential is first initated (when the voltage gated sodium channels open) and lasts until the Inactivation Gate on the voltage gated sodium channel reOPENS)

The relative refractory period is the period in which it is possible to generate another action potential, but requires a greater than normal stimulus BECAUSE the voltage gated potassium channels are still open (so any depolarization would be “nullified” by more potassium efflux) and the membrane potential is in an undershoot. So the relative refractory period starts when the voltage gated sodium channel is “De-Inactivated” and ends when the voltage gated potassium channels close and RMP is restored.

3. At the top of the rising phase (when voltage gated K+ channels open) in what direction do the electrical and chemical gradients point respectively for K+ ?

Both the chemical and electrical gradients point out of the cell, so there is a strong driving force for potassium efflux when voltage gated potassium channels open at the top of the rising phase…this allows for a rapid restoration of the resting membrane potential.

4. If an action potential was engaged in a debate with a graded potential, what would it assert as the fundamental differences between the two parties? (see attached table)

(SEE TABLE 12-4 IN THE TEXTBOOK)

5. What is the difference between continuous vs. saltatory conduction?

Continuous Conduction occurs in unmyelinate axons. The action potential is propagated along the entire length of the axon as adjacent regions of the axolemma are depolarize by opening of voltage gated sodium channels.

Saltatory Conduction occurs in myelinated axons and is FASTER as the depolarization can leap across the internode (myelinated region) to the next Node of Ranvier.

6. What does it mean for the action potential to be “non-decremental” and “all-or-none”?

The strength of depolarization during any action potential is the same and does not decease over distance (it is the same strength at the axon terminal as it is at the initial segment) = non-decremental. Action potentials are not graded – they either occur or they do not (all-or-none). The textbook gives a nice metaphor – if you squeeze the trigger of a gun sufficiently hard the gun will fire…it does not matter if you squeeze 10 times harder than you need to the gun will fire at the same intensity.

7. What is the evolutionary significance of myelination?

It allows us to propagate neuronal information more rapidly and with less space occupied by the axon. If all of our axons were unmyelinated and still propagated information as rapidly, the diameter of each axon would have to be many times greater…the combined effect of this means that our spinal cords would be many feet in diameter! Not very practical… Myelination Rules!

8. Concept application: If you experimentally depolarized a resting axon beyond threshold half-way along the axon, an action potential would propagate bidirectionally….both towards the soma (backpropagation) and towards the synaptic terminal(s). Under actual physiological conditions, when an action potential is initiated at the initial segment of the axon, there is no backpropagation observed despite the fact that influx of sodium ions at that same point in the axon would theoretically depolarize all adjacent regions of the membrane. Why? (Be brief but specific).

Although all adjacent regions of the axon-plasma membrane (axolemma) are depolarized when sodium channels open, the regions of the axolemma that are closer to the soma are still in the absolute refractory period, so the action potential only goes in the forward direction and does not backpropagate.

Synaptic Transmission:

1.Describe the sequence of events that takes place when an axon potential arrives at the synaptic terminal.

1) Action potential arrives at pre-synaptic nerve terminal

2) Voltage Gated Calcium Channels are activated (open).

3) Calcium ion influx causes neurotransmitter containing vesicles (which are ‘tethered’ to the active zone of the inner side of the pre-synaptic membrane at rest) to fuse to the membrane and dump their contents (exocytosis) into the synaptic cleft.

4) Neurotransmitter molecules diffuse across the synaptic cleftand bind to receptors on the post-synaptic membrane. The consequence of this binding depends on the properties of the given receptor. It can either result in the opening of an ion channel or the activation of an intra-cellular signaling cascade (see below)

5) Neurotransmitter is cleared from the synaptic cleft. In the model shown for Acetylcholine (ACh), an enzyme called acetylcholine-esterase rapidly degrades ACh into choline and acetic acid. Acetic acid is more dispensable and gets absorbed by near-by glial cells. Choline is more precious and is endocytosed into the pre-synaptic terminal for recycling into more ACh. Note that for other neurotransmitters other mechanisms may exist for clearing the NT from the synapse, including endocytosis by astrocytes.

2. What is the major type of synapse in the nervous system and what are three anatomical types of neuron-neuron synapses?

The major type of synapse is the chemical synapse (involving communication via neurotransmitter diffusion across a small distance between the presynaptic and postsynaptic membrane)

1) Axo - Dendritic

2) Axo – Somatic

3) Axo – Axonic (as in presynaptic facilitation or presynaptic inhibition)

3. Define the following: EPSP, IPSP, temporal summation, spatial summation, shunting inhibition (as a class)(ignore), presynaptic facilitation, presynaptic inhibition.

EPSP:Excitatory Post Synaptic Potential. A graded potential that causes depolarization (more positive). Typically via activating Sodium Channels

IPSP:Inhibitory Post Synaptic Potential. A graded potential that causes hyperpolarization (more negative). Typically via activating Potassium or Chloride Channels

Temporal Summation:Multiple stimulations (graded potentials) occurring at the same synapse over a period of time. They SUM together to create a large “splash” in the membrane potential.

Spatial Summation:Multiple stimulations (graded potentials) occurring at the same time at multiple sites along the soma/dendrite that SUM together to alter the membrane potential.

Presynaptic Facilitation: An axon terminal of the presynaptic neuron synapses on the axon terminal of the post-synaptic neuron, and the activity at that synapse leads to INCREASEDactivity at the voltage gated calcium channels in the post-synaptic cell such that arrival of an action potential in that cell will result in MORE neurotransmitter release.

Presynaptic Inhibition: An axon terminal of the presynaptic neuron synapses on the axon terminal of the post-synaptic neuron, and the activity at that synapse leads to REDUCEDactivity at the voltage gated calcium channels in the post-synaptic cell such that arrival of an action potential in that cell will result in LESS neurotransmitter release.

4. Which types of signaling molecules (neurotransmitters/neuromodulators/hormones) would have cytosolic receptors and which would have membrane receptors?(Slides 139 - 41)

Large and polar neurotransmitter / neuromodulators / hormones (including amino acids, amine-derived, and peptides) have plasma membrane receptors since they cannot traverse the membrane in order to initiate changes inside the target cell.

Small and/or nonpolar signaling molecules can freely traverse the plasma membrane thus they have cytosolic receptors.

5. What is the significance of metabotropic receptors? Of neuromodulation?

Metabotropic receptors involve the coupling of receptor activation to an intracellular signaling cascade, that can result in the opening or closing of an ion channel, and/or the activation/inactivation of gene transcription, and/or the activation/inactivation of certain enzymes and metabolic pathways. The significance is that diverse events that must happen in concert among these three types of cellular activity can be activated simultaneously through stimulation at one type of receptor, which is more efficient.

6. What is the significance of research using neuro-toxic chemicals?

It allowed for the elucidation of the different ion channels and overall secretory mechanisms involved at synapses.

Multiple Choice:

1. The activation of ligand-gated ion channels is always associated with:

  1. Generation of action-potentials
  2. Change in the permeability to an ion
  3. Depolarization
  4. Hyperpolarization

2. If you were an axon establishing a new connection with another neuron, where would you want to establish that synapse to have to most profound impact on the frequency with which that neuron fires action potentials?

  1. Dentritic Branches
  2. Dentritic Spines
  3. The Axon Hillock
  4. The Axoneme

3. The absolute refractory period is due to:

  1. Inactivation of voltage-gated sodium channels
  2. Prolonged opening of voltage-gated potassium channels
  3. Prolonged opening of potassium leakage channels
  4. Inactivation of sodium leak channels

4. During an action potential, activity at which type of channel is responsible for the rapid restoration of the resting membrane potential after depolarization has occurred?

A. Potassium leak channels

B. Voltage-gated sodium channels

C. The Na+/K+ ATPase

D. Voltage-gated potassium channels1.

5. All of the following are associated with activity at a chemical synaptic terminal except:

A. Rough Endoplasmic Reticulum

B. Gap Junctions

C. Voltage Gated Calcium Channels

D. Mitochondria

6. Atropine from deadly nightshades blocks certain receptors (muscarinic) for acetylcholine. Cholinergic neurons will still be capable of all of the following functions except:

A. Propagating Action Potentials

B. Clearing Acetylcholine from the Synaptic Cleft

C. Generating PSP’s on Target Cells Containing Muscarinic Receptors

D. Releasing Acetylycholine into the Synaptic Cleft

7. Neurons requiring the highest rate of communication with the CNS or target tissues will probably utilize:

A. Large, Myelinated Axons

B. Small, Myelinated Axons

C. Small, Non-Myelinated Axons

D. Large, Non-Myelinated Axons

8. At a particular axosomatic synapse, repeated action potentials arrive at the synaptic terminal of the presynaptic neuron. In the post-synaptic neuron, you will observe:

A. A combination of depolarization and hyperpolarization

B. Temporal Summation

C. Spatial Summation

D. An Immediate Action Potential

9. A toxin is present in sufficient amount to block 20% of Potassium leak channels in the dendrites and soma of a neuron. Which of the following would you expect as a result?

A. The cell cannot fire action potentials

B. The resting membrane potential will be more negative

C. It will be easier to achieve above threshold stimulation of the neuron

D. The relative refractory period will be longer

1