Synaptic Transmission

Question 1

Synaptic Transmission

Answer 1

Processes involved in transfering an electrical signal across a specialized gap between two electrically excitable cells

Electrical Synapse and Chemical Synapse

Question 2

The electrical synapse

Answer 2

Discription:

A distinct transcellular spcae exists between the pre and post synaptic cell membranes - gap junction

Structure:

Presynaptic cell terminal membrane is sealed to postsynaptic cell membrane in the region of the gap junction by intercelllar strucutres called “connexons

• provides a cytoplasmic link (low resistance) without time delay

Physiological functions

extremely fast pathways for bidirecitonal transfer of electrical signals through CNS

• reliable and use very little metabolic energy
• interconnect inhibitory neruons

Question 3

Chemical Synapse - Structure

Answer 3

Transcellular discontinuity exists between pre and postsynaptic nerve or muscle cell membrane

• at synapse, membranes are separated by a true extracelluar space
• cytoplasm of terminal region of presynaptic cell contains numerous spherical, sealed membrane bound “synaptic vesicles” that vary from 40-200 nm

Question 4

Ionotropic Receptors

Answer 4

Inotropic receptor on postsynaptic cell membrane

Receptor is part of the ion channel

• combination of NT with the receptor leads to immediate opening of the ion channel - very rapid

Classic exmaple of postsynaptic Ach receptor channel at vertebrate skeletal muscle nueromuscular junction

1. Ach binds to receptor leads to increse in Pk and PNa
2. Local, non-propogated depolarization of the muccle fiber end plate region
3. receptors were initially called nicotinic receptors because they were activated by nicotine

Question 5

Metabotropic receptor

Answer 5

A G protein-coupled receptor

• Combination of NT with receptor causes activation of membrane receptor bound G protein complex
• Also know as the muscarinic receptor since was shown to be activated by muscarine (found in mushrooms)

In cardiac atrial muscle:

• release of B gamma subunit complex of the G protein causes K+ channel to open and membrane hyperpolarization
• This slows the generation of APs in the SA node and thus heart rate

Question 6

Skeletal Neuromuscular Transmission

Answer 6

1. APs propagated to the peripheral termianl of the axon
2. Each of terminal branch end forming a “bouton” that synapses on a single muscle fiber
   
   1. Motor unit = branched axon with its innervated msucle riber
   2. all muscle fibers are activated simultaneously
3. Neuromucular transmission is inititaed by the AP generated depolarization at the presynaptic terminal
   
   1. depolariation causes an opening of voltage-sensitive Ca2+ channels in the presynaptic nerve terminal membrane
   2. and an uptake of Ca from the ECF in the synaptic cleft
4. Increased Ca2+
   
   1. releases vesicles bound to retiuclar sites in presynaptic cell cytoplasm
   2. fusion of synaptic vesicle membrane to the presynaptic terminal membrane (opening of bound vesicles)

Question 7

Synaptic Cleft

Answer 7

• 50 nm wide
• The basal lamina portion of this extracellular matrix functions to maintain a stable junciton between pre and postsynpatic membranes
• Acetylcholinc esterase enzyme is essential for hydrolyzing Ach into choline and acetate
  
  • terminates the generation of AP’s and active force in sketleal muscle fibers

Question 8

Postsynaptic Electrophysiological Responses

Answer 8

Under normal physiological conditions the amplitude of the EPP is always five to ten times greater than the muscle fiber threshold potential required to produce the AP

• A one to one relationship exists between generation of an End Plate Potential and an AP in the skeletal muscle fiber

Question 9

Curare

Answer 9

A toxin that is a competitive inhibitor of ACh binding at the nicotinic Ach receptor

Question 10

Myesthenia Gravis - muscle weakness

Answer 10

Significant loss of functional Ach receptors in the muscle end plates

• results from an autoimmune disease that produce antibodies that compete with ACh for its binding site on the Ach receptor

Question 11

Botox and Tetanus toxins

Answer 11

These toxins block specific proteins that mediate the binding of vesicles to the terminal membrane of the presynaptc nuerons in the spinal cord

• thus preventing the release of NTs into the synpatic cleft

Botox:

• inhibition of release of ACh from vesicles in excitatory presynpatic neurons innervating motor neurons - weakness/paralysis
• inhibition of cholinergic neurons in the ANS to cause disturbance in every organ system whose function under ANS

Tetanus

• Block of NT release primarily from inhibitory neurons that inhibit excitatory activity in motor neurons
• Abnormal increase in excitiary motor neruon activity leading to muscle rigidity

Question 12

Synaptic Transmission in the Nervous System

Answer 12

• The presynaptic axon terminals are called boutons
• Dendritic spines are short branches that extend from the dendrite of the postsynaptic cell
• Long term potentiation - enhancement of the postsynaptic response resulting from an increased excitatory input (responsible for memory)

Question 13

Spatially focusd synaptic networks

Answer 13

• Small groups of neurons that form “dedicated” neuronal circuites for specific body functions
• Designed for specific, fast and focused activities

Question 14

Widely divergent synaptic networks

Answer 14

• Axons that make widely dispersed and diffuse synpatic connections to neurons in multiple sections of the brain
• essential for modulating level of arousal, motor control, memory, mood etc..
• targets of most psychiatric drugs

Question 15

Excitatory synapses

Answer 15

Increase in excitability of postsynaptic cell located in the brains visual cortext

• excitatory NTs at fast excitatory synapses in the brain is either glutamate or aspartate
  
  • synapses termed “glutaminergic”

Question 16

Excititory Post Synaptic Potental (EPSP) vs. End Plate Potential (EPP)

Answer 16

Similarity

• both dependent upon an increase in membrane conductance of both Na and K
• EPSP - opening of glutamate-activated channels in postsynaptic nerve terminal and EPP - opening of the ACh nicotinic cholingergic receptor channels in the skeletal muscle end plate

Difference:

• Amplitude of the EPSP generated at a single synapse in the post synpatic neuron is only .01 mV - a few mV
• amplitude of the EPP generate in muscle motor end plate is ~40mV
• Thus generation of an AP requires spatial and or temporal summation of many subthreshold EPSPs (at many excitatory synapses) on the postsynaptic neruon

Question 17

Inhibitory Synapses

Answer 17

Decrease in excitability of a postsynaptic cell body located in the brain’s visual cortex

1. Inhibitory NTs are either GABA or glycine
2. Both bind to receptors that open Cl- selective channels
   
   1. Inhibitory in CNS because E-Cl is near or more negative than the resting potential
3. Incrase in Cl conductance will produce a local hyperpolarization (IPSP - Inhibitory post synaptic potential) that will reduce cell excitability

Question 18

Voltage clamping

Answer 18

Postsynaptic cell membrane is clamped to 0 mV, the amplitude of the EPSP is zero

• At 0 mV, the Na current is equal and opposite to the outward K current
• This potential is termed the reverse potential because at resting membrane potentials greater than 0 mV the EPSP changes from a depolarization to a hyperpolarization

If the postsynaptic cell membrane is clamped to -71 mV (equilibrium potential for Cl-)

• amplitude of the IPSP will be zero
• since the net Cl current will be zero