006 Neuronal Signaling and Synaptic Transmission

Question 1

• list the types of transient electrochemical signals used by neurons to interact with each other

Answer 1

o	Porduced by brief alterations in the electrochemical properties of the cell membrane that give rise to the resting membrane potential
o	3 types
	Generator (receptor) potentials
	Action potentials
	Post-synaptic potentials

Question 2

• explain how the cell membrane acts as a capacitor

Answer 2

o the cell membrane maintains separation of charge between the inside of the cell and the outside because it acts as a permeability barrier to the diffusion of ions
 Ions cannot freely diffuse across the cell membrane

Question 3

• describe the ion channels important for neuron function, including types and gated vs. non-gated

Answer 3

o Channels
 Protein structure in cell membrane that selectively allows something to move across the membrane
 allow hydrophilic ions to travel through the hydrophobic membrane
o Under tight control by a neuron
o Gated channels
 Have a molecular gate that can be opened or closed
 Voltage gated channels
• Can be open or closed based on changes in voltage across the channel
 Ligand-gated channels
• Open or closed by the attachment of some sort of ligand (smaller molecule that binds to a larger molecule)
• Example: channel closed or opened by neurtransmitters
o Non-gated channels (AKA leakage channel)
 Have NO gates
 Are always open
 Always allow things to cross the membrane based on diffusion principles
o For this section these ion channels matter most
 Na Channels
 K Channels
 Cl Channels

Question 4

• explain the resting membrane potential

Answer 4

o The unequal distribution of ions across the cell membrane
o -65 mV inside the cell
o Concentrations
 Na
• More OUTside
 CL
• More OUTside
 K
• More INside
 Organic anions (mostly protein)
• More INside
• Cannot diffuse at all
o The total concentrations of K, Na and Cl are roughly equal
o The relative membrane permeabilities of these three ions are most important in determining resting membrane potentials
 Involves diffusion so the number of non-gated channels are important
o K is the most permeable ion through the cell membrane
 Has the most non-gated channels
 Trying to get out of the cell along concentration gradient and trying to get into the cell along the electrical gradient
 Resting membrane potential of neuron is closest to Nernst potential of K (since K is the leakiest of involved ions)
o Na is somewhat permeable through the cell membrane
 Has quite a few non-gated channels, but NOT as many as K
 Always trying to get into the cell by passive fluc along both concentration and electrical gradients
 This makes resting potential slightly more positive than the Nernst potential for K
o **Nernst potential = voltage produced across a membrane by a concentration gradient of an ion that can diffuse across the membrane while oppositely charged ions cannot pass through the membrane
 In the case of neurons they are the organic anions

Question 5

• explain the importance of the Na+/K+ pump to the maintenance of the resting membrane potential

Answer 5

o Serve to pump sodium OUT the cell and potassium INTO the cell
o Balances the passive fluxes of these ions while the cell is at rest
 The ions around a neuron are in a steady state but NOT at equilibrium
 In most neurons, the pump is electrogenic
• Creates a resting membrane potential more negative than if it just balanced the passive fluxes of Na and K
o Cl has NO active fluxes, so it exists at equilibrium
Due to a large number of non-gated channels (but not as many as K)

Question 6

• explain how the resting membrane potential is a local phenomenon associated only with the cell membrane

Answer 6

o Bulk concentrations of ions barely change in the neuron as a whole
o Membrane potentials are a local phenomenon at the membrane only
o Changes in membrane potential are caused by changes in permeability to these ions

Question 7

• explain the action potential

Answer 7

o AKA nerve impulse
o The active signal used by neurons to convey information
o Electrochemical phenomena (NOT electricity)
 So the time for ions to diffuse is an important factor
 Slows down the rate, but it is still a very fast phenomena (a few milliseconds)
o Very rapid
 Speed of an action potential is the conduction velocity
 Based on membrane capacitance and axial resistance
o All or none principal
o Transient
o Self-propagating
 Travels in one direction down the length of the axon
 Due to the sequential voltage changes opening and closing the voltage gated channels along the axon
o Absolute refractory period
 The point where another action potential cannot be generated
 Occurs during the repolarization phase (when K is flowing out of the cell)
 Ends once the neuron reaches resting potential
o Relative refractory period
 Occurs during hyperpolarization
 Another action potential can be generated but the threshold is higher than normal
• A stronger stimulus is needed to open enough Na channels to initiate another action potential

Question 8

• describe the sequence of events associated with an action potential, including channel openings and closings, ion fluxes, and membrane potential changes

Answer 8

o A stimulus (i.e. synaptic transmission and generator potential) depolarizes the cell membrane
 Makes the inside positive enough to reach threshold in the region of the initial segment of the axon
 At threshold, triggers the K gated channels to BEGIN opening
o Voltage gated Na channels open
 Allows Na to rapidly flow into the cell
 Causes an inward Na current
 Results in the voltage inside the cell to become positive (depolarized)
 Two things happen with this positive potential
• Na voltage-gated channels close to stop the influx of Na
• K voltage gated channels are completely open and K now flows rapidly out of the cell
o Results in negative potential inside the cell (repolarization)
o Movement is so rapid that the cell gets more negative than resting potential (hyperpolarized; hyperpolarization afterpotential)
o K voltage-gated channels close due to the more negative potential inside the cell
 Stops the efflux of K out of the cell
o Once all of the voltage gated channels are closed the cell rapidly restores resting membrane potential
 Uses the Na/K pumps

Question 9

• explain the concept of conduction velocity and the variables involved in its determination

Answer 9

o the measurable speed at which an action potential travels along an axon
o not the same for all axons
o dependent upon
 membrane capacitance
• the functional thickness of the axon membrane
• thicker=faster
o thicker wall means less ion leakage (less capacitance)
 axial resistane
• related to axon diameter
• larger=faster
o smaller surface area/volume ratio=less axial resistance

Question 10

• explain saltatory conduction along a myelinated axon

Answer 10

o occurs in myelinated axons
o myelin serves to
 make the axon membrane thicker
• decreases capacitance
 increase the effective diameter of the axon
• decreasing resistance
o Makes conduction MUCH faster
o Myelin has NO ion channels so it blocks the self-propagating nature of the action potential
 The A.P. would diminish to nothing in a short distance if the myelin was continuous
 Nodes of Ranvier is where the axon membrane has ion channels and has access to the intracellular substances
• Necessary for periodic regeneration of the action potential
o A.P. jumps from node to node

Question 11

• explain electrical synapse transmission

Answer 11

o synaptic cleft exits between two neurons such that neurons do not actually connect with each other
o Electrical is NOT common in human nervous systems
o For practical purpose gap junctions
o A very narrow synaptic gap (20 nm)
o Have connexons that bridge the intercellular space
 Depolarization of one neuron directly depolarizes the next (voltage-gated phenomenon)
o ALWAYS an excitatory phenomenon
o Very little delay at the synapse
o Synapse may be bi-directional
o Example
 Intercalated discs in myocardium

Question 12

• explain chemical synapse transmission

Answer 12

o most common type of synapse
o use neurotransmitters that diffuse across the synaptic cleft to affect the next neuron in line
o have a wider synaptic cleft than electrical synapses (about 50 nm)
o Specific sequence of events that occur at a chemical synapse in order for it to communicate with the next neuron
 Neurotransmitters are stored in synaptic vesicles in the pre-synaptic cleft
 Depolarization from an action potential reaches the synapse and opens voltage gated Ca channels in the cell membrane of the pre-synaptic terminal
 Ca flows into the neuron
 Ca cause synaptic vesicles to fuse with the cell membrane and release neurotransmitters into the synaptic cleft
 Neurotransmitters diffuse across the cleft
 Ligand-gated ion channels with an associated receptor on the post-synaptic membrane bind the neurotransmitter
 The ligand-gated ion channel opens or closes (changes from its resting state)
• If normally closed it will open and allow ion flux to occur
• If normally opened it will close and stop ion flux from occurring
 Neurotransmitter is released from the receptor with the change from resting state of the channel (when it opens or closes)
 Once released, the ligand-gated channel returns to its resting condition
 As long as the nuerotransmitters remain in the synaptic cleft, they can keep binding to receptors

Question 13

• describe the sequence of events involved in a chemical synaptic transmission, including the roles of the action potential, Ca++ and its voltage-gated channels, neurotransmitters, and the ligand-gated channels

Answer 13

o Specific sequence of events that occur at a chemical synapse in order for it to communicate with the next neuron
 Neurotransmitters are stored in synaptic vesicles in the pre-synaptic cleft
 Depolarization from an action potential reaches the synapse and opens voltage gated Ca channels in the cell membrane of the pre-synaptic terminal
 Ca flows into the neuron
 Ca cause synaptic vesicles to fuse with the cell membrane and release neurotransmitters into the synaptic cleft
 Neurotransmitters diffuse across the cleft
 Ligand-gated ion channels with an associated receptor on the post-synaptic membrane bind the neurotransmitter
 The ligand-gated ion channel opens or closes (changes from its resting state)
• If normally closed it will open and allow ion flux to occur
• If normally opened it will close and stop ion flux from occurring
 Neurotransmitter is released from the receptor with the change from resting state of the channel (when it opens or closes)
 Once released, the ligand-gated channel returns to its resting condition
 As long as the nuerotransmitters remain in the synaptic cleft, they can keep binding to receptors

Question 14

• describe the various ways that synaptic transmission is terminated

Answer 14

o Diffusion of neurotransmitter out of the synaptic cleft
 Usually NOT a significant factor
o Pre-synaptic cell re-uptakes neurotransmitters for recycling
o Enzymatic action (usually from surrounding glial cells) cause degradation of the neurotransmitter

Question 15

• describe the two (2) types of post-synaptic potentials : excitatory and inhibitory

Answer 15

o Excitatory post-synaptic potential (EPSP)
 Makes the potential inside the neuron more positive
o Inhibitory post-synaptic potential (IPSP)
 Makes the potential inside the neuron more negative

Question 16

• list the common neurotransmitters and the usual type of post-synaptic potential that they produce

Answer 16

o	post-synaptic potentials are graded (NOT all or none)
o	Acetylcholine
	Action (excitatory or inhibitory) depends on the type of receptor in the post-synaptic neuron
•	Nicotinic receptor
o	Common in PNS
o	Excitatory
•	Muscarinic receptor
o	More common in the CNS
o	Can be excitatory or inhibitory depending on where they are found
o	Biogenic amines
	Catecholines
•	Norepinephrine - excitatory
•	Dopamine – excitatory
	Seratonin
•	Inhibitory
o	Amino acids
	Glutamate
•	Excitatory
	Aspartate
•	Excitatory
	Gamma aminobutyric acid (GABA)
•	Most common inhibitory NT
	Glycine
•	Inhibitory
o	Neuroactive peptides
	A lot that isn’t covered in this course

Question 17

• explain the concept of threshold when it comes to initiating an action potential

Answer 17

o membrane potential where voltage-gated Na channels are opened (AP is initiated)
 important because whether or not it reaches the threshold is the main factor in determining whether or not that neuron sends an AP to the next neuron
o For most neurons threshold is -45 mV inside the cell
o Important only where the axon attaches to the axon hillock (initial segment)
 First place where there are voltage-gated channels in the neuron (not in the soma)

Question 18

• explain how the summation of synaptic inputs determines whether or not threshold is achieved (and its consequences either way)

Answer 18

o The number of synapses creating post-synaptic potentials
 More synapses=more effect
o Types of synapses that are stimulated
 Excitatory vs. inhibitory
o How rapidly the synapses are stimulated (temporal summation)
 Faster=more effect
o Location of synapse in relation to initial segment (spatial summation)
 Post-synaptic potentials only have an effect on the cell membrane for a relatively short distance
 The closer the synapse is to the initial segment, the more likely it is to affect membrane potential at that location
o The amount of transmitter released at a synapse
 More transmitter more effect
 Can be affected by axoaxonic synapses

Question 19

• explain temporal summation, spatial summation, pre-synaptic facilitation, and pre- synaptic inhibition

Answer 19

o Temporal summation
 How rapidly the synapses are stimulated
o Spatial summation
 Location of the synapse in relation to the initial segment
o Pre-synaptic inhibition
 Axoaxonic synapses decreases the amount of neurotransmitter released
 Quite common
o Pre-synaptic facilitation
 Less common the inhibition
 Axoaxonic synapse increases the amount of neurotransmitter released at a syanpse

Question 20

• explain the generator potential

Answer 20

o Only occur at sensory receptors that are true neurons
o They are how a receptor transduces a stimulus into a neural phenomenon
o Similar to post-synaptic potentials (always graded)
o Caused by modality specific stimulus to a receptor that changes the resting state of modality-gated ion channels
o When generator potentials affect enough modality-gated ion channels that threshold is reached, an action potential is initiated and is carried toward the CNS

Question 21

• list common modalities that stimulate modality-specific channels in sensory receptors

Answer 21

o Photoreceptors – light photons
o Mechanoreceptors – change in shape of receptor
o Thermoreceptors – change in temperature
o Chemoreceptors – specific chemicals (i.e. H)