Events at The Neuromuscular Junction

Sending the Message

Now!  Here is where we get to put all those parts into motion.  You should review the anatomyThe study of the structure of the human body. of the neuromuscular junctionThe connection between a motor neuron and a muscle fiber. minilecture before viewing this one.  This area is where neuronsThe functional cells of the nervous system that transmit signals. and muscles come so close that only moleculesGroups of atoms bonded together. can fit between them. In this space, the neuron is part of the nervous systemThe organ system that controls body functions using electrical and chemical signals.. It sends an action potentialA rapid, temporary electrical charge that travels along neurons, allowing signal transmission., or electricity, to a muscle fiber (the fancy name for muscle cell).  Muscle fibers, although part of the muscular systemThe organ system responsible for movement and heat production. specialized for contraction, can still be excited by a neuron.

Let’s send the message from the neuron to the muscle fiber.  To accomplish this, we need to manipulate numerous ion channelsProtein passages in the cell membrane that allow specific molecules to pass through. in the membranes. These include ligand gated, voltage gated, and all kinds of gated channels.  Make sure to revisit our topic of cell membranes in a previous chapter. It will help you review these types of ion channels and understand how and when they open.  Wiggle your big toe.  You have sent an action potential from your brain. It traveled down your spinal cordThe central nervous system structure that relays signals between the brain and body.. Then, it went out through your sciatic nerveThe largest nerve in the body, arising from the sacral plexus., which is hurting me right now. Finally, it reached the muscles in your toe.  As that action potential moves through the membrane of the neuron, it reaches the end. This end is called the axon terminalThe endpoint of an axon where neurotransmitters are stored and released into a synapse..  On the axon terminal are channels that open when they receive electricity. They allow calcium cations to flow into the axon terminal. The calcium cations cause the vesicles of acetylcholinealso know as ACh A neurotransmitter that stimulates muscle contraction. to fuse with the neuron’s membrane. The vesicles then pour out into the synapseThe junction between two neurons where communication occurs. via exocytosisThe process of expelling materials from a cell via vesicles that fuse with the plasma membrane.. This is another term from that previous chapter to which we are constantly referring. 

At this point, the neuron is like, “I’m out.” The neuron has released its chemical messenger into the synapse. That neurotransmitterChemicals that transmit signals across synapses., acetylcholine, is floating across the synapse via diffusionPassive movement of molecules from areas of high to low concentration..

Receiving the Message

As the neurotransmitter acetylcholine diffuses across the synapse, there are a few fates that it can endure.  It’s intended fate is to connect to a ligand-gated channel, with the ligand being acetylcholine in this case.   There are tons of these ligand-gated channels in the neuromuscular junction. The rest of the sarcolemma is crowded with voltage-gated channels, much like the calcium ones on the neuron. Acetylcholine never enters into the muscle fiber.  I can’t stress that enough!  Acetylcholine is like a token that gets deposited into the turnstile but never enters the subway.  Acetylcholine attaches itself to the active siteThe specific region of an enzyme where a substrate binds and a reaction occurs. of the protein receptorA structure that detects stimuli.. This opens the channel portion of the protein. 

But, what, then, does move into the cell?  Or does something move out of the cell?  At first, sodium(Na⁺): Major ECF cation; important for fluid balance, nerve function. moves in because it is more concentrated on the outside of the cell. It is attracted to all the negatively charged proteinsLarge molecules made of amino acids with various functions in the body. in a cell.  This moment when those channels open and sodium moves in is key.  This is the start of electricity in the muscle fiber.  This is called excitement.  This does not guarantee a muscle contraction.  In factA statement based on direct observation that is repeatedly confirmed., this just causes a change in voltage at the motor end plateThe part of the muscle fiber membrane involved in neuromuscular transmission..

Propagating the Message

When sodium enters a cell, the cell becomes more positively charged.  We call this depolarizationThe loss of electrical charge across a membrane, triggering an action potential..  Just like a body temperature or any other set point, a cell has a voltage at which it sits.  If it is encouraged to take on sodium, the cell will depolarize.  You want me to say the opposite thing here.  No.  If a cell is encouraged to release potassium(K⁺): Major ICF cation; essential for muscle and nerve function., the cell will repolarize or become more positive.  Or can I say “less negative?”  Do you find these terms slightly confusing?  I do.  This is why I usually draw this model of a cell I am sure you have seen me draw before. 

We have these Ach-ligand-gated protein channel receptorsProteins located on the surface or inside cells that bind specific molecules (e.g., neurotransmitter open. Sodium is moving into the cell. So much sodium moves into the cell that PING!  These other channels, away from the motor end plate start to open too.  These are voltage-gated channels, but they work the same in terms of sodium and potassium.  Now think of this in 3D.  One neuron have many axon terminals that meet with motor end plates scattered along the muscle.  Each of these spots depolarizes at the same time and this wave spreads through the muscle.  This is not excitement.  This is propagation or conductionThe transmission of nerve impulses along neurons..  This is moving that initial excitement away from its origin and also applying a bit of positive feedbackA control mechanism that amplifies a change instead of reversing it. in there.

Myasthenia Gravis

Let’s talk about a disease and then let’s talk about muscle relaxers.

This picture on the left here is great.  It kinda sums it up with a picture very much like the one we drew.  This disease, myasthenia gravis is a neuromuscular disorder that results in muscle weakness..  Like, I can’t breathe muscle weakness.  A rogue B cell in the bone marrow decides to make an antibody. This occurs, similar to many auto-immune diseases. This antibody is not quite right.  It has a region that can attach to the ACH receptors and block the transmission of the action potential.  These antibodies here are literally standing in the way of acetylcholine.

Muscle relaxers that work at the neuromuscular junction do the same thing.  They block the transmission of the action potential.  You can do this in so many ways, not just by binding up the receptors.  You could create a molecule that prevents the exocytosis of the acetylcholine.  You could create a molecule that blocks the calcium channels on the axon terminal.  There are lots of ways to fiddle with the neuromuscular junction so that the action potential is not passed. 

That is muscle relaxers, but what about re-stimulating the muscles of the people inflicted with these diseases?  That’s a good question to which one of you should answer after going into research at a pharmaceutical company.  There is an enzyme that removes Ach from the synapse.  It is called acetylcholinesterase.  We can stop it from degrading Ach. This may allow Ach to spend more time in the synapse. This potentially increases the possibility of connecting with a ligand-gated channel.