House of Mind

"Biology gives you a brain. Life turns it into a mind" - Jeffrey Eugenides

  • 31st July
    2011
  • 31
The Neuromuscular Junction (NMJ) is a specialized synapse that serves to transmit electrical impulses (action potentials) from the motor neuron nerve terminal to the skeletal muscle. Basically, the NMJ allows for efficient and reliable communication between the motor neuron nerve and the muscles required for contraction and movement. The primary chemical messenger in this synapse, which consists of the presynaptic region (containing the nerve terminal), the synaptic cleft and the postsynaptic surface, is acetylcholine. These regions are defined by the differential localization of specific proteins, which underlie their distinct anatomical features and their physiological roles.  Now it’s time to briefly sum up what goes on in the NMJ, as shown in the diagram above.  1. The action potential (or electrical impulse signal) reaches the nerve terminal in the presynaptic region. The hallmark feature of the nerve terminal is that it contains the synaptic vesicles, along with the proteins that help vesicle function. These vesicles are aligned near their release site, called an active zone.  2. When action potentials reach the nerve terminal they activate calcium channels, which open up and facilitate the influx of calcium into the presynaptic terminal, which in turn commences the process of vesicular release into the synaptic cleft.  3. The increase in intracellular calcium concentration triggers the fusion of the synaptic vesicles with the nerve terminal membrane. The mechanism of synaptic vesicle fusion involves conformational changes in multiple docking proteins both on the vesicle and the nerve terminal’s plasma membrane.  4. Once fused with the nerve terminal membrane, the vesicle releases its contents into the extracellular space, also known as the synaptic cleft. The chemical or neurotransmitters (in this case, acetylcholine) released then bind to their corresponding receptors on the postsynaptic surface (also known as the motor end plate in the NMJ).  5 & 6. Acetylcholine binds to its receptors and opens ligand-gated Na+/K+ channels. These structures are designed to optimize cholinergic neurotransmission in order to produce an end plate potential (EPP). The EPP is simply the net synaptic depolarization caused by the release of acetylcholine triggered by the nerve action potential. The EPP is a function of the miniature endplate potential (MEPP) amplitude, which represents the depolarization of the postsynaptic membrane produced by the contents of a single vesicle, and quantal content (number of transmitter vesicles released by a nerve terminal action potential. The EPP serves to open the voltage-gated Na+ channels in the postsynaptic region, which in turn results in an action potential that triggers muscle fiber contraction. These changes in the postsynaptic region potential result in muscle stimulation and contraction. 7. Acetylcholinesterase degrades acetylcholine so that it (choline) can be re-uptaked and recycled to produce new acetylcholine molecules. It’s activity terminates synaptic transmission.  Sources: Hughes, Benjamin W., et. al. 2006. Molecular architecture of the neuromuscular junction. Muscle & Nerve. 33(4): 445-461. DOI 10.1002/mus.20440 Motor Systems: Control of Movement and Behavior. 2008. Available at: http://www.colorado.edu/intphys/Class/IPHY3730/09motorsystems.html

The Neuromuscular Junction (NMJ) is a specialized synapse that serves to transmit electrical impulses (action potentials) from the motor neuron nerve terminal to the skeletal muscle. Basically, the NMJ allows for efficient and reliable communication between the motor neuron nerve and the muscles required for contraction and movement. The primary chemical messenger in this synapse, which consists of the presynaptic region (containing the nerve terminal), the synaptic cleft and the postsynaptic surface, is acetylcholine. These regions are defined by the differential localization of specific proteins, which underlie their distinct anatomical features and their physiological roles. 

Now it’s time to briefly sum up what goes on in the NMJ, as shown in the diagram above. 

1. The action potential (or electrical impulse signal) reaches the nerve terminal in the presynaptic region. The hallmark feature of the nerve terminal is that it contains the synaptic vesicles, along with the proteins that help vesicle function. These vesicles are aligned near their release site, called an active zone. 

2. When action potentials reach the nerve terminal they activate calcium channels, which open up and facilitate the influx of calcium into the presynaptic terminal, which in turn commences the process of vesicular release into the synaptic cleft. 

3. The increase in intracellular calcium concentration triggers the fusion of the synaptic vesicles with the nerve terminal membrane. The mechanism of synaptic vesicle fusion involves conformational changes in multiple docking proteins both on the vesicle and the nerve terminal’s plasma membrane. 

4. Once fused with the nerve terminal membrane, the vesicle releases its contents into the extracellular space, also known as the synaptic cleft. The chemical or neurotransmitters (in this case, acetylcholine) released then bind to their corresponding receptors on the postsynaptic surface (also known as the motor end plate in the NMJ). 

5 & 6. Acetylcholine binds to its receptors and opens ligand-gated Na+/K+ channels. These structures are designed to optimize cholinergic neurotransmission in order to produce an end plate potential (EPP). The EPP is simply the net synaptic depolarization caused by the release of acetylcholine triggered by the nerve action potential. The EPP is a function of the miniature endplate potential (MEPP) amplitude, which represents the depolarization of the postsynaptic membrane produced by the contents of a single vesicle, and quantal content (number of transmitter vesicles released by a nerve terminal action potential. The EPP serves to open the voltage-gated Na+ channels in the postsynaptic region, which in turn results in an action potential that triggers muscle fiber contraction. These changes in the postsynaptic region potential result in muscle stimulation and contraction.

7. Acetylcholinesterase degrades acetylcholine so that it (choline) can be re-uptaked and recycled to produce new acetylcholine molecules. It’s activity terminates synaptic transmission. 

Sources:

Hughes, Benjamin W., et. al. 2006. Molecular architecture of the neuromuscular junction. Muscle & Nerve. 33(4): 445-461. DOI 10.1002/mus.20440

Motor Systems: Control of Movement and Behavior. 2008. Available at: http://www.colorado.edu/intphys/Class/IPHY3730/09motorsystems.html

  • 25th February
    2011
  • 25
Axoplasmic Transport of Neurotransmitter Vesicles Simply put, axonal transport is the cellular mechanism responsible for transporting or trafficking cell parts to and from the cell body, or soma. Many proteins and particularly vesicles are made in the cell body but are needed elsewhere in the neuron. Naturally, this ability to transport essential cell components back and forth from the axon is critical for the neuron’s ability to survive, grow and function. So how exactly do vesicles move? Conveniently enough, they get help from “motors” that are made up of complex protein interactions. Like I mentioned before, transport in the neuron is bidirectional, and different motor protein complexes are associated with a particular direction.  Kinesins take care of forward (anterograde) transport while dyneins take care of backward (retrograde) transport. Lastly, motor protein complexes need something to be “anchored” to, right? That’s where microtubules come in. Microtubules provide the tracks along which these motor proteins move along “carrying” the vesicle or other cell parts.  Once the vesicles are where they need to be (usually in the synaptic cleft), other things like neurotrophic factors may assist in vesicular release and re-uptake related to synaptic transmission. 

Axoplasmic Transport of Neurotransmitter Vesicles

Simply put, axonal transport is the cellular mechanism responsible for transporting or trafficking cell parts to and from the cell body, or soma. Many proteins and particularly vesicles are made in the cell body but are needed elsewhere in the neuron. Naturally, this ability to transport essential cell components back and forth from the axon is critical for the neuron’s ability to survive, grow and function.

So how exactly do vesicles move? Conveniently enough, they get help from “motors” that are made up of complex protein interactions. Like I mentioned before, transport in the neuron is bidirectional, and different motor protein complexes are associated with a particular direction.  Kinesins take care of forward (anterograde) transport while dyneins take care of backward (retrograde) transport. Lastly, motor protein complexes need something to be “anchored” to, right? That’s where microtubules come in. Microtubules provide the tracks along which these motor proteins move along “carrying” the vesicle or other cell parts. 

Once the vesicles are where they need to be (usually in the synaptic cleft), other things like neurotrophic factors may assist in vesicular release and re-uptake related to synaptic transmission.