Exam 2- AP transmission Flashcards
AP transmission is defined as the movement of an AP from __ to __…
from the membrane of one excitable cell to the membrane of another
neuronal transmission is defined as the movement of an AP from __ to __…
from the terminals of one neuron to the dendrites of another neuron
neuromuscular transmission is defined as the movement of an AP from __ to __…
from the terminals of a neuron to the membrane of a muscle cell
describe the basis of neuromuscular transmission and the structures involved
physical basis of neuromuscular transmission lies in connection of nerve terminal membrane and muscle membrane
- nerve terminal membrane ends in a swelling called the terminal button, this comes very close to the membrane of the muscle, but there’s a space b/w them
- this arrangement is called the neuromuscular junction or the motor end plate (motor end plate is large and complex end-formation by which the axon of a motor neuron establishes synaptic contact with muscle cell
- the space between terminal and muscle membrane is called synaptic cleft
the AP has to jump from terminal membrane to muscle, how does this happen?
transmitted by a mechanism (cannot just jump thru space)
- nerve terminal has a typical sodium pump, Na and K channels, and resting potential of -70 mV
- also has a calcium ATPase pump which uses energy of ATP to pump calcium out of terminal to outside space –> this creates a large calcium concentration (high conc outside and low conc inside terminal membrane)
- also has voltage-gated calcium channels- at rest, these are gated/closed
- inside terminal are synaptic vesicles which contain a chemical substance belonging to a class of neurotransmitters (acetylcholine, Ach)
where are neurotransmitters synthesized?
either in cell body (peptides that can serve as neurotransmitters, synthesized in rough ER, packaged by Golgi, and trafficked and sit in nerve terminal button)of presynaptic neuron OR terminal button itself…it just depends
describe when Ach is synthesized in the terminal button itself
Coenzyme A taken up by mitochondria and comes out as acetyl-CoA
- Acetyl-CoA and choline combined –> acetylcholine, packaged in presynaptic vesicle
- synaptic vesicles also have other transporters- has a proton ATPase and a hydrogen ATPase
- proton ATPase uses ATP tp pump protons into the vesicle –> the protons then tend to diffuse out across vesicle membrane, transport proteins exchange protons for Ach (Ach into vesicle for protons out of vesicle)
once AP travels down axon and depolarizes membrane of nerve terminal button, what happens?
this activates voltage-sensitive calcium channels at terminal button –> calcium enters the cell and calcium current then activates a process that results in migration of vesicles to the terminal button membrane and the opening of vesicles to dump the Ach by exocytosis
- how does calcium do this…? calcium activates snare proteins (a set of complementary proteins- one protein on synaptic vesicle called synaptobrevin and in terminal button membrane is SNAP-25 and syntaxin)
- calcium activates these, changes shape and they twist, which pulls synaptic vesicle to the membrane, the 2 membranes fuse –> synaptic vesicle opens and dumps Ach in synaptic cleft by exocytosis (the Ach diffuses across synaptic cleft and binds to Ach receptor on surface of muscle- the nicotinic receptor)
name of the Ach receptor and why that is its name
nicotinic receptor (the receptor will bind either Ach or the plant substance nicotine)
- discovered pharmacologically, nicotine has same effect as Ach, so the receptors are named for the drug that was first used to document its presence
describe the structure and function of nicotinic receptor
large transmembrane complex- made of 5 subunits: 2 alpha, 1 beta, 1 delta, 1 gamma (form a circle and inside circle is sodium channel)- forms a sodium channel in muscle membrane
- alpha subunits each have a binding site for Ach (Ach binds to each of the alpha subunits), when 2 Ach bind –> the complex changes shape and the Na+ channel is activated –> inward directed Na+ current across the muscle membrane (if enough of the nicotinic receptor Na+ channels activated, depolarization of muscle membrane is enough to take it to threshold- this depolarization to threshold is called an end plate potential) –> threshold reached, voltage changes voltage-gated sodium channels on the membrane
overall: takes 2 Ach binding to nicotinic receptor to activate Na+ channel
what kind of receptor is the Ach nicotinic receptor?
ligand-gated channel (ligand is Ach)
Ach belongs to a class of neurotransmitters, which indirectly…
carries AP across synaptic cleft
AP’s carry very specific pieces on information, when AP transmitted from nerve to muscle, info has to stay intact, it needs a ___
1:1 correspondence of AP’s in nerve and muscle to keep info the same
what happens as soon as Ach diffuses across the synaptic cleft and causes an end-plate potential?
Ach is broken down by enzyme called Ach esterase, which has 2 isoforms in neuromuscular junction:
1- AchE-R: (read-through isoform), unanchored and soluble in synaptic cleft itself, this isoform is all along protein filaments
2- AchE-S: (synaptic isoform), anchored to muscle membrane in association with nicotinic receptor
describe how much Ach is needed to cause 1 AP and its association with the 2 isoforms
it takes about 200 synaptic vesicles being released from the nerve terminal to release enough Ach to diffuse across the membrane and cause an AP (each synaptic vesicle contains 50,000 molecules of Ach –> so takes 10 MILLION MOLECULES OF ACH RELEASED FROM NERVE TERMINAL TO GENERATE 1 AP ON MUSCLE)
- most of the 10 million go to saturating the AchE-R isoform, so most are broken down before it even gets across the synaptic cleft (makes sure just the right amount of Ach makes it through to interact with Ach(nicotinic) receptors
