1.

In the space below draw a neuro-muscular junction, and identify the important physiological
structures discussed in class. Using your drawing, explain in detail how one nerve action
potential causes one muscle action potential. Lastly, compare and contrast the physiological
effects of curare vs. nerve gas (i.e. a cholinesterase inhibitor).

The neuro-muscular junction is an area between the terminal buttons of the lower motor neurons
and the motor end plate on the sarcolemma of a myofiber. As the action potential travels into the
terminal button of the lower motor neuron the cell depolarizes. The VGCaC opens allowing CA to rush
inside the cell. The CA binds to the synaptotagmin proteins located on synaptic vesicles. These
vesicles contain 10,000 molecules of Acetylcholine and are located in the terminal buttons. As Ca
binds to synaptotagmin it allows the v snare proteins on the vesicles to bind to the t snare proteins
located on the phospholipids bilayer of the terminal button. The synaptotagmin proteins insert into the
bilayer and pull the vesicles to the membrane where ACH is then released. This process is known as
exocytosis.
Located on the motor end plate of the sarcolemma are multiple ACH receptors (proteins). Two ach
molecules released from the terminal buttons, bind to Ach receptors. The Ach receptors open,
allowing for NA to pass through the channel changing the electrical charge from -80 mv to -50 mv
(threshold). After the muscle action potential is made there is an enzyme in the synapse called
cholinesterase (Achase) which breaks down Ach into acetic acid and choline allowing the Ach
receptors to close.
This overall process converts one electrical impulse from the motor neuron into a chemical signal
in the neuromuscular junction back to one muscle action potential.
Curare is a drug that lasts 15 min. It looks and acts like Ach. Therefore when curare is injected in
the body, it binds to the Ach receptors preventing the channel to open. In turn, this causes flaccid
paralysis because the muscle is unable to convert the chemical signal to a muscle action potential.
Sarin and VX gas act as Achase inhibitors. These inhibitors blocks cholinesterase which doesnt
allow the Ach receptor to close, causing uncontrolled amounts of action potentials. This results in
spasmodic paralysis. VX gas is used in the military and is 10x stronger than Sarin gas.
- terminal button
o synaptic vesicles containing ACH
o synaptotagmin and V snares connected to vesicles
o T snares are connected to the phospholipids bilayer
o VGCAC voltage gated calcium channels
o VGNAC
o VGKC
o Resting potential = -80 mv
o Where exocytosis occurs
o High K
o Low Na
- Muscle cell (myofiber)
o Sarcolemma phospholipid bilayer
o Motor end plate one per cell
o Ach receptors act as NA channels

2. In the space below draw a sarcomere and identify all of the important structures discussed in
class. Next, use your drawing to explain, in detail, how a muscle action potential causes
contraction via the sliding filament theory. Also, explain the physiological rational for rigor
mortis. Lastly, compare and contrast fast twitch and slow twitch muscle.
Sarcomere:
- actin
- myosin
- z-line
- titin
- troponin
- tropomyosin
sarcoplasmic reticulum (on top)
- terminal cisternae
- SERCA
- RYR (ryanodine channel)

The muscle action potential travels down the t-tubules located on the sarcolemma. The t-tubules form a
triad at the z-line of the sarcomeres along with terminal cisternae. In the absence of calcium ions,
tropomyosin blocks access to the mysosin binding site of actin. In a resting muscle calcium is pumped
from the extracellular fluid into the terminal cisternae via SERCA, a protein in the longitudinal SR.
During a muscle AP triggered by the depolarization of t-tubules, the RyR at the terminal cisternae of
the SR allow calcium to diffuse out. The calcium then binds to troponin. When calcium binds to
troponin, the positions of troponin and tropomyosin are altered on the thin flament and myosin then
has access to its binding site on actin.
Myosin in the presence of ATP undergoes a change to a high-energy state. The myosin head
binds to actin at 90 degrees forming a cross-bridge between the thick and thin filaments. The energy
stored by myosin is released along with ADP and inorganic phosphate. A power stroke occurs when
the myosin heads (attached to the actin) move from 90 deg to 45 deg. ADP is converted to ATP
allowing for myosin heads to release the actin. The myosin heads then recover to 90 deg and ATP is
converted to ADP by myosin ATPase. The process repeats 10nm from the last pull. When the calcium
level decrease, troponin locks tropomyosin in the blocking position and the thin filament slides back to
the resting state.
Rigor mortis occurs after death when your flexors and extensors contract at the same time. This
happens because there is no more ATP in the muscle and SERCA cannot pump Ca into the terminal
cisternae. Ca then leaks out of the SR and binds to troponin. ADP on the myosin heads allows the
heads to bind to actin, but because there is no CA being pumped or ATP, the heads cannot power
stroke. This causes a permanent crossbridge. Rigor mortis takes about 6 hours to set in.
Fast twitch muscle fibers take 50 ms to contract. The fibers are white/pale in color. Fast twitch
muscle have twice as many S.R. and have fast isoforms of myosin ATPase therefore breaking down
ATP 4 times faster than slow twitch muscles. They use glycolysis to make ATP from ADP. This
process is anaerobic meaning it does not use oxygen. It has a product of lactate and H+. These end
products cause fatigue because they block RyR, preventing Ca to be released.
Slow twitch muscle fibers take 200 ms to contract (also known as time to peak tension) and are
red in color. Unlike fast twitch muscles, slow twitch muscles do not fatigue because they contain twice
as many mitochondria which convert ADP-ATP aerobically. The end products are CO2 and H20 and
do not cause fatigue because they do not form lactic acid.
3. In the space below draw a typical nerve action potential, and identify the important components
discussed in class. Next, explain in detail the physiological mechanisms (diffusion,
concentration gradients, gates. etc) responsible for causing an action potential. Lastly, compare
and contrast conduction in myelinated vs. unmyelinated neurons.

The nerve action potential which is an electrical impulse, begins with the upper motor neuron
located in the motor cortex of the brain. If it is located on the right side of the brain the neuron will
travel to the opposite sidethe left sideof the body. This is known as decussation. The dendrite of
the upper motor neuron receives an impulse from the motor cortex. When the dendrite receives this
impulse it travels from the dendrite to the cell body to the axon hillock. This is the first place on the
neuron where VGNAC and VGKC are located allowing for action potential. The cell is first resting at -
80 mv with a high concentration of K inside the cell and high concentrations of NA outside the cell. As
the impulse hits the cell it reaches -50 mv also known as threshold. This opens the VGNAC of the
neuron for 1ms. During this time Na is able to diffuse into the cell causing depolarization where the
cell reaches a 0 mv charge and then into overshoot where the cell is positive 30 mv. At 30 mv the
VGNAC closes and the VGKC opens for 2 ms and potassium diffuses out of the cell. The cell
repolarizes to -90 mv. At this stage hyperpolarization is reached and prevents the action potential from
going backwards in the cell only allowing a continuous forward motion. The whole process takes 4 ms
to complete. The action potential travels down the axon of the upper motor neuron which is located in
the lateral white matter of the spinal cord. The action potentials continue to the collaterals (about 10
per neuron and are myelinated) of the neuron to the terminal buttons (unmyelinated). The terminal
buttons synapses with the dendrites of the lower motor neuron in the ventral horn of the grey matter in
the spinal cord therefore transferring the impulse. The upper motor neurons terminal buttons and the
lower motor neurons dendrites do not come in direct contact they are about 10 nm apart. In total there
are also about 25 billion neurons.
An action potential has a velocity of 1m/s in unmyelinated neurons; however myelin has
increased the conduction velocity to 100 m/s. This is because no action potential occurs under the
myelin which is wrapped around the axon of the neuron. Each axon is 95% myelinated. The action
potential occurs in gaps between the myelin known as nodes of ranvier. The action potentials cannot
occur under myelin because myelin blocks the NA and K pump. This is known as saltatory conduction.