SKELETAL MUSCLE FIBER PHYSIOLOGY

Excitability of Muscle Fibers

Muscle fibers, like other cells, can generate electrical signals. When the brain or
spinal cord sends signals along nerves to muscle fibers, they contract. These
cells, like others, have a negative charge inside compared to the outside, creating
an electrical difference across their membranes.
Ion Channels
The cell membrane's interior is hydrophobic, making it difficult for charged
particles, especially ions, to move across it. However, the electrical properties of
skeletal muscle cells rely on ion movement through ion channels. There are two
main types of ion channels: leak channels, which allow ions to slowly leak across
the membrane even in resting cells, and gated channels, which are crucial for
generating action potentials in stimulated cells.
The Resting Membrane Potential
Electrically excitable cells, like neurons and muscle fibers, have an electrical
charge difference across their membranes even at rest, known as the resting
membrane potential. This potential is maintained by three main factors: higher
concentration of potassium ions inside (lower) the cell, higher concentration of
sodium ions outside (upper) the cell, and greater permeability of the membrane
to potassium than to sodium ions.
Measuring the Resting Membrane Potential
The image illustrates how the resting membrane potential of a muscle cell is
measured and the mechanisms involved in generating it. It measured by using An
oscilloscope measures the resting membrane potential in skeletal muscle. It
works by displaying a graph of electrical signals over time.
Measurement Setup:
An electrode is inserted into a muscle cell membrane to measure the voltage
difference between the inside and the outside of the cell.
The measured potential is displayed on an oscilloscope, which shows a negative
value (approximately -85 mV Millivolts), indicating that the inside (lower) of the
cell is negatively charged relative to the outside (upper).
Generation of the Resting Membrane Potential.
The resting membrane potential is primarily generated by the following factors:
1. Uneven Distribution of Ions:
● There is an unequal distribution of ions across the cell membrane.
● Inside(lower) of the cell, there are higher concentrations of
potassium ions (K⁺) and negatively charged proteins (Pr⁻).
● Outside (Upper) of the cell, there are higher concentrations of
sodium ions (Na⁺).
*Kaya siya tinawag na Uneven Distribution of Ions dahil hindi siya equally
distributed sa inside (lower) and outside (upper) part of the cell.
2. Potassium (K⁺) Leak Channels:
● The cell membrane allows K⁺ ions to pass through easily because it
has many K⁺ leak channels .
● K⁺ ions tend to move out of the cell, down their concentration
gradient, making the inside of the cell more negative.
*Kapag mas madaming K+ ions mas mabilis silang makakapasok at mas
nagging negative ang inside (lower) part ng cell.
3. Sodium (Na⁺) Leak Channels:
● There are also Na⁺ leak channels, but they are less numerous
compared to K⁺ channels.
● Na⁺ ions tend to move into the cell, down their concentration
gradient, but the permeability is lower than that for K⁺, thus
contributing less to the resting potential.
*Si Na+ ions kapag mas madami sila may isang aalis at pupunta sa Inside
(lower) part ng cell, dahil si Na+ ions ay mostly attracted sila sa fewer sodium+
ions. So, even though si sodium ions nagmove sa Inside (lower) part ng cell,
which is located si Potassium ions, hindi naman nakapagcocontribute si sodium
ions sa negative side ng Potassium ions, kumbaga Saling Pusa lang si Sodium
Ions.
4. Sodium-Potassium (Na⁺/K⁺) Pump:
● The Na⁺/K⁺ pump actively transports 3 Na⁺ ions out of the cell and 2
K⁺ ions into the cell, using ATP for energy.
● This pump helps to maintain the concentration gradients of Na⁺ and
K⁺ across the membrane and contributes to the negative resting
 membrane potential by expelling more positive charges sodium ions
(Na⁺) than it brings in potassium ions (K⁺).

Action Potentials
An action potential happens when a cell is stimulated, causing a reversal of the
resting membrane potential, making the inside positively charged. This reversal
occurs due to ion channels opening, allowing ions to move across the membrane,
leading to depolarization and repolarization phases.

Gated Ion Channels and the Action Potential

1. Resting Membrane Potential:

● When the cell is at rest, there are more sodium ions (Na⁺) outside
(Upper) the cell and more potassium ions (K⁺) inside (Lower) the cell.
.
● The inside (lower) of the cell is more negatively charged compared
to the outside (Upper), creating what is called the resting membrane
potential.
2. Depolarization:
● When a muscle cell is stimulated, ligand-gated sodium (Na^+)
channels open, allowing Na^+ to enter and depolarize the cell (make
it more positive). If this depolarization reaches the threshold level,
(Threshold means limit) it triggers an action potential, which causes
more sodium channels to open, further increasing the positive
charge inside the cell and initiating muscle contraction.
*Basically charge change (CC) siya, from negative turning to positive membrane
potential.

3. Repolarization:
● As the cell becomes positive, it triggers permeability changes,
halting depolarization and beginning repolarization. Repolarization
occurs when Na+ channels close and K+ channels open, causing K+
to leave the cell and restoring its negative charge. This process ends
the action potential, and the sodium-potassium pump returns the
cell to its resting state.
The Neuromuscular Junction (NMJ):
● The NMJ is a special connection where a motor neuron meets a muscle
fiber.
● This junction allows the nerve signal to pass from the neuron to the
muscle, causing the muscle to contract.
Function of the neuromuscular junction (NMJ):
1. Opening of Ca2+ channels
● When a nerve signal Action Potential (AP) travels down a motor
neuron's axon and reaches the end (presynaptic terminal), it causes
calcium (Ca²⁺) channels in the cell membrane to open. allowing Ca²⁺
to flow into the axon terminal.
2. Exocytosis of synaptic vesicles
● Once inside the cell, the calcium (Ca²⁺) ions trigger a few synaptic
vesicles to release their contents into the synaptic cleft through a
process called exocytosis.
3. Release of ACh
● ACh is released into the synaptic cleft through the process of exocytosis.
4. Binding Of ACh
● The Acetylcholine (ACh) molecules move across the synaptic cleft and
attach to ligand-gated sodium (Na⁺) channels in the sarcolemma (the
muscle cell membrane), causing these channels to open.
5. Opening of ligand-gated sodium (Na⁺) channels
● Sodium ions move into the muscle fiber, leading to depolarization.
what is Depolarization?....... Charge change (CC) siya, from negative turning to
positive membrane potential.
● When the depolarization in the muscle fiber reaches a certain level
(threshold), it triggers an Action Potential (AP) in the muscle fiber.
6. Closing of Na⁺ channels
● Acetylcholine (ACh) stops attaching to the gated sodium (Na⁺) channels,
causing them to close.
7. Breakdown of Acetylcholine (ACh)
● Acetylcholinesterase quickly breaks down acetylcholine in the synaptic
cleft into acetic acid and choline.
 ● Ang trabaho ni Acetylcholinesterase is prevents acetylcholine from
building up in the synaptic cleft, where it could constantly stimulate the
motor end-plate and cause continuous muscle contraction.
8. Reabsorption of Choline
● Motor neurons bring choline molecules back into the axon terminal.
● These choline molecules then mix with acetic acid inside the neuron to
make acetylcholine (ACh)
9. Production of new Acetylcholine (ACh)
Energy Efficiency:
● Instead of constantly making new acetylcholine, Mas convenient na Ireuse
si choline molecules para mas mabilis and less energy ang gagamitin.
● The acetylcholine molecules are then picked up by small storage
compartments called synaptic vesicles. ready for the next round of
neurotransmission.

Muscle contraction
Action potentials in the outer layer of skeletal muscle fibers trigger muscle
contraction by initiating the mechanical aspect. This connection happens at the
triad, where calcium ions (Ca2+) are stored in the sarcoplasmic reticulum. The
release of acetylcholine at the neuromuscular junction induces an action
potential in the muscle's outer layer, starting the contraction process.

Summary of Skeletal Muscle Contraction.

1. Action Potential in neuron:
● An electrical signal (action potential) travels along the motor neuron.
2. Opening of voltage-gated Ca2+ Channels:
● The action potential triggers the opening of calcium (Ca²⁺) channels.
3. Acetylcholine Release:
● Ca²⁺ rushes into the motor neuron, prompting the release of
acetylcholine.
4. ACh opens Na2+ channels:
● Acetylcholine opens sodium (Na⁺) channels in the muscle cell
membrane (sarcolemma).
5. Action Potential Generation:
● This leads to an action potential in the muscle fiber, spreading
across its surface.
 6. Action Potential down T - Tubule:
● Action potentials also travel down T tubules, which are like tunnels
running deep into the muscle fiber.

7. Release of Ca2+ from Sarcoplasmic Reticulum:

● The action potentials reach the sarcoplasmic reticulum, a calcium
Ca2+ storage unit within the muscle fiber, causing it to release
stored calcium ions into the surrounding sarcoplasm.
8. Ca2+ binds to Troponin Activation:
● Calcium binds to troponin, a protein on the actin filaments, which
causes tropomyosin to move and expose binding sites on actin.
● Cross-Bridge Formation: Myosin heads attach to these binding sites
on actin, forming cross-bridges.
9. ATP breakdown drives myosin head power stroke:
● ATP molecules are then used to "fuel" the movement of the myosin
heads, which pull the actin filaments towards the center of the
sarcomere, resulting in muscle contraction. As long as calcium is
present, this cycle repeats, allowing for sustained muscle
contraction.

Cross-bridge movement:
1. Exposure of active sites:
● Myosin heads, part of the thick filaments in muscle cells, store
energy from the breakdown of ATP during the previous contraction
cycle. They stay in a resting position until the muscle is stimulated
by a nerve signal.
2. Cross-Bridge formation:
● When calcium ions (Ca^2+) bind to troponin, it exposes attachment
sites on the thin filaments (actin). This prompts the myosin heads to
quickly bind to these sites.
3. Power Stroke:
● This binding forms cross-bridges between the thick and thin
filaments, triggering a rapid movement of the myosin heads. This
movement, called the power stroke, pulls the actin filaments towards
the center of the sarcomere, causing muscle contraction.
4. Cross-Bridge release:
 ● Binding of ATP to the myosin head causes it to detach from actin,
allowing for relaxation of the muscle fiber.

5. hydrolysis of ATP:
● ATP is then broken down into ADP and phosphate (P), which remain
attached to the myosin heads, providing energy for the next
contraction cycle.
6. Recovery Stroke:
● The myosin heads return to their resting position through a recovery
stroke. This restores them to a high-energy state, ready for another
cycle of attachment to actin and contraction. This process continues
as long as calcium and ATP are available, allowing for sustained
muscle activity.