NJN 4. Musculoskeletal

• This section explains how acetylcholine stimulates a muscle cell to develop an endplate potential and eventually an action potential.

Synaptic Cleft

• The space between the neuron and the muscle cell is the synaptic cleft.
• Acetylcholine diffuses across the synaptic cleft from high to low concentration after being released by exocytosis.

Postjunctional Folds

• The muscle cell membrane is folded where the neuron binds, creating postjunctional folds.
• Postjunctional folds increase the surface area for the muscle cell to receive the stimulus from the motor neuron.

Ligand-Gated Ion Channels

• The muscle cell membrane contains abundant ligand-gated ion channels, specifically nicotinic receptors.
• A ligand is a substance that binds to a channel protein and facilitates a change; in this case, the ligand is acetylcholine.
• Nicotinic receptors are a specific type of ligand-gated ion channel, specifically type one.
• These receptors are pentameric proteins, consisting of five protein subunits: two alpha, one beta, one delta, and one gamma.
• They can be written as A2 beta delta gamma protein.

Resting Membrane Potential

• Cells have a resting membrane potential, which is a voltage developed inside the cell membrane compared to the outside.
• Skeletal muscle cells typically have a resting membrane potential of approximately -90 millivolts, which is more negative than neurons (-70 mV).
• Resting membrane potential is maintained by:
  • Sodium-potassium pumps (Na+/K+ ATPases)
  • Passive potassium leakage channels

Sodium-Potassium Pumps (Na+/K+ ATPases)

• Three sodium ions are pumped out of the cell, while two potassium ions are pumped into the cell.
• More positive ions leave than enter, contributing to a more electronegative charge inside the cell.
• This process requires ATP and is a primary active transport.
• Sodium concentration is higher outside the cell, while potassium is higher inside the cell.

Potassium Leakage Channels

• Potassium ions move from high to low concentration (inside to outside) through passive, always-open channels.
• As more positive potassium ions leave, the cell becomes even more electronegative, helping maintain resting membrane potential.

Acetylcholine Binding and Ion Flow

• When acetylcholine binds to nicotinic receptors, the channels open.
• Sodium ions flow into the cell down their concentration gradient, and potassium ions flow out down their concentration gradient.
• More sodium ions flow in than potassium ions flow out, making the inside of the cell more electropositive.

Endplate Potential (EPP)

• The change in the cell's potential due to ligand-gated ion channels makes the inside of the cell more positive.
• The endplate potential brings the membrane voltage from the resting membrane potential (-90 mV) towards the threshold potential.
• Every excitable cell has a threshold potential, which in skeletal muscle cells is approximately -55 mV.

Voltage-Sensitive Sodium Channels

• These channels have two gates: an inactivation gate and an activation gate.
• Once the membrane potential reaches threshold (-55 mV), the activation gate opens.
• Sodium ions rush into the cell.

Depolarization and Action Potential

• As sodium rushes in through voltage-sensitive sodium channels, the inside of the cell becomes extremely positive.
• The membrane potential reaches a peak of approximately +30 mV.
• This influx of positive charges constitutes depolarization, leading to an action potential

Sodium Channel Inactivation

• Once the membrane potential reaches +30 mV (peak depolarization), the inactivation gate closes, blocking sodium from entering.
• The action potential spreads across the sarcolemma (muscle cell membrane).

Transverse Tubules (T-tubules)

• These are invaginations of the sarcolemma T-tubules allow the action potential to spread into the muscle fiber.

Dihydropyridine Receptors

• Located on the T-tubules, these receptors are stimulated by the positive charges moving along the T-tubules.
• They are also known as voltage-sensitive calcium channels, or L-type calcium channels.
• Dihydropyridine receptors are mechanically coupled to ryanodine receptors on the sarcoplasmic reticulum.

Sarcoplasmic Reticulum (SR)

• The SR is a specialized derivative of the endoplasmic reticulum, rich in calcium.
• Enlarged sacs of the SR are called terminal cisternae.

Triad Structure

• In skeletal muscle, a triad consists of a T-tubule with sarcoplasmic reticulum on both sides.

Ryanodine Receptors

• These receptors are located on the sarcoplasmic reticulum membrane (specifically type one).
• When the dihydropyridine receptor is stimulated, it pulls on the ryanodine receptor, opening a channel.
• This allows calcium to flow out of the sarcoplasmic reticulum into the sarcoplasm.
• Calcium then binds to troponin, initiating the sliding filament mechanism for muscle contraction.

Calcium Release and Muscle Contraction

• Positive ions accumulating across the T-tubule membrane activate dihydropyridine receptors.
• Activated dihydropyridine receptors pull on ryanodine receptors, opening calcium channels.
• Calcium floods out of the sarcoplasmic reticulum and binds to troponin, initiating the sliding filament theory.

Repolarization

• At the peak of depolarization (+30 mV), the activation gate on potassium channels opens.
• Potassium ions rush out of the cell, causing the inside of the cell to become more electronegative.
• Potassium efflux continues until the cell reaches its resting membrane potential (approximately -90 mV).
• The inactivation gate on potassium channels then closes.

Key Terms

• Sarcolemma: The plasma membrane of a muscle cell.
• Endomysium: Connective tissue covering the sarcolemma.
• T-tubule: Invagination of the sarcolemma.
• Sarcoplasmic Reticulum: Specialized endoplasmic reticulum for calcium storage.
• Terminal Cisternae: Enlarged sacs of the sarcoplasmic reticulum.
• Triad: Two sarcoplasmic reticula and a T-tubule.
• Calsequestrin: A protein within the sarcoplasmic reticulum that binds calcium.
• Depolarization: The process where the cell becomes more positive due to sodium influx.
• Repolarization: The process where the cell returns to a negative voltage due to potassium efflux.