Chapter 10. Directly Gated Transmission At The Nerve-Muscle Synapse

Front 1

What are two major types of chemical transmission?

Back 1

Direct and indirect

Front 2

What is the best system to study direct receptors?

Back 2

The neuromuscular junction

Front 3

What are the benefits of studying the neuromuscular junction?

Back 3

The muscle cell is large enough to accommodate several microelectrodes for electrophysiological measurements

Postsynaptic membrane can be visualized with the light microscope in a living cell

Muscle fiber is innervated by only one motor axon

Front 4

What is the transmitter released at the neuromuscular junction?

Back 4

ACh

Front 5

What receptor type is in the muscle membrane?

Back 5

The nicotinic type of ACh receptor

Front 6

What is the end-plate?

Back 6

The motor neuron's axon innervates this specialized region of the muscle membrane

Front 7

Does the axon have myelin at its end?

Back 7

No

Front 8

Does the axon branch?

Back 8

Yes

Front 9

What are synaptic boutons?

Back 9

Multiple grape-like varicosities that are the ends of the branches of the axon, where transmitter is released

Front 10

What are junctional folds?

Back 10

A depression in the surface of the muscle fiber where the membrane of the muscle fiber forms deep folds; corresponds to a bouton

Front 11

What is the basement membrane?

Back 11

Basal lamina; lines the junctional folds; a network of connective tissue consisting of collagen and glycoproteins that covers the surface of the entire muscle fiber

Front 12

Which cell secretes secretes proteins into the basement membrane?

Back 12

Both the presynaptic and muscle cell

Front 13

Describe acetylcholinesterase.

Back 13

Enzyme that inactivates the ACh released by the presynaptic terminal by hydrolyzing it to acetate and choline

Front 14

What organizes the synapse?

Back 14

The basement membrane

Front 15

What machinery is required in the presynaptic  bouton to release transmitter?

Back 15

1) Synaptic vesicles, which contain ACh

2) Active zone, a membrane specialization

3) Voltage-gated Ca2+ channels

Front 16

What is the function of calcium in the presynaptic terminal?

Back 16

It triggers the fusion of the synaptic vesicles with the terminal

Front 17

What part of the presynaptic terminal is apposed to the junctional fold?

Back 17

The active zone

Front 18

Characterize the crest of the junctional fold.

Back 18

Receptors for ACh are clustered

Front 19

Describe the depths of the folds.

Back 19

Rich in voltage-gated Na+ channels, which convert the end-plate potential into an action potential

Front 20

What is the name of the excitatory postsynaptic potential at the neuromuscular junction?

Back 20

End-plate potential

Front 21

What is the amplitude of the endplate potential?

Back 21

70 mV

Front 22

What is the amplitude of the typical synaptic potential from a single neuron?

Back 22

Less than 1 mV

Front 23

What would you use to block ACh channels?

Back 23

Curare

Front 24

What is the purpose of adding curare to the NMJ?

Back 24

To reduce the end-plate potential so that it doesn't trigger an action potential

Front 25

What are the kinetics of the NMJ response to a subthreshold end-plate potential?

Back 25

Rises rapidly but decays more slowly

Front 26

What two processes act quickly to remove ACh from the cleft?

Back 26

1) ACh is hydrolyzed by the acetylcholinesterase

2) ACh diffuses away, out of the synaptic cleft

Front 27

How can you determine which ions move through the membrane to produce synaptic action?

Back 27

By systematically changing the membrane potential and determining the reversal potential for synaptic action

Front 28

What is reversal potential?

Back 28

The membrane potential at which the synaptic potential or synaptic current has zero amplitude

Front 29

What is the equation for current of the excitatory post-synaptic potential?

Back 29

Iepsp = gepsp x (Vm - Eepsp)

Front 30

What is the reversal potential for the end-plate?

Back 30

0 mV

Front 31

What determines the reversal potential for the end-plate?

Back 31

A weighted average of ENa and Ek

Front 32

How do Na+ and K+ transmitter-gated and voltage-gated channels differ in the NMJ?

Back 32

1) Move through different classes of voltage-gated channels, one for each, activated sequentially; the ACh-activated channel is large enough for either to pass with equal selectivity, also Ca2+

2) Na+ flux in the voltage-gated channels is regenerative, ACh channel activation is limited by the amount of ACh available and cannot produce an all-or-none action potential

3) Pharmacological differences, TTX blocks voltage-gated Na+ but not transmitter-gated, alpha-bungarotoxin blocks ACh receptors only

Front 33

What determines the reversal potential?

Back 33

1) Relative conductance for the permeant ions

2) The equilibrium potentials of the ions

Front 34

What two things are balanced at the reversal potential?

Back 34

INa + Ik = 0

Front 35

Describe a double-gated channel.

Back 35

NMDA receptor, both chemically and voltage gated

Front 36

What technique would you use to measure the current through a single ACh-activated channel?

Back 36

Patch-clamp

Front 37

What effect does changing the driving force have on the current?

Back 37

The magnitude of the current through the channels

Front 38

What is the equation for total synaptic conductance?

Back 38

gEPSP = n x gamma

where n is the average number of channels opened, defined by n = N x po where po is the propability that any given ACh channel is open and N is the total number of ACh channels

Front 39

What is the equation for total end-plate current?

Back 39

IEPSP = N x po x gamma x (Vm-EEPSP)

Front 40

What four factors does the current for the end-plate potential depend on?

Back 40

1) The total number of end-plate channels

2) The probability that a channel is open

3) The conductance of each open channel

4) The driving force that acts on the ions

Front 41

What determines the probability that a transmitter-gated channel is open?

Back 41

The concentration of the transmitter at the receptor, not the value of the membrane potential

Front 42

What two functions does a directly gated receptor-channel have?

Back 42

1) It recognizes and binds the chemical transmitter

2) It opens a channel in the membrane through which ion flows

Front 43

Which subunit of the nicotinic ACh receptor binds ACh?

Back 43

Alpha

Front 44

What determines the cation-selectivity of the nicotinic receptor?

Back 44

Three rings of negative charge that flank the M2 region

Front 45

What are the three regions of the receptor-channel complex?

Back 45

1) A large entrance region at the external membrane surface

2) A narrow transmembrane pore that may determine cation selectivity

3) A large exit region at the internal membrane surface

Front 46

What is the net effect of the opening of nicotinic ACh receptors?

Back 46

Net influx of Na+ ions

Front 47

What are the three parallel regions of the end-plate equivalent circuit?

Back 47

1) A branch representing the flow of synaptic current through the transmitter-gated channels

2) A branch representing the return current flow through nongated channels (the nonsynaptic membrane)

3) A third branch representing current flow across the lipid bilayer, which acts as a capacitor

Front 48

What are two parallel pathways for outward current flow?

Back 48

1) Nongated channels

2) Capacitive pathway

Front 49

What is the equation for membrane voltage?

Back 49

(gEPSP x EEPSP + gm x Em) / (gEPSP + gM)

Front 50

What is the equation for the amplitude of the end-plate potential?

Back 50

deltaVEPSP = Vm - Em