NJN 5. Skeletal Muscle Contraction: Action Potentials & Calcium

Skeletal Muscle Contraction: Overview

• The notes cover skeletal muscle contraction, detailing the transmission of action potentials, the role of acetylcholine, and the release of calcium.
• The information explains the coupling of these processes with the actual contraction activity.

Action Potential Transmission

• Somatic motor neurons in the anterior/ventral grey horn of the spinal cord fire, producing action potentials that move down the axon.
• Voltage-gated sodium channels open, allowing sodium to flow in, causing a depolarizing current.
• Sodium is responsible for bringing the membrane potential to threshold.
• As positive ions flow into the cell, the inside becomes more electropositive.

Role of Calcium

• Positive charges moving across the synaptic bulb stimulate proteins responsible for bringing calcium in.
• Calcium acts as a cross-link between synap proteins (Snap 25, Syntaxin, Synaptobrevin, Synaptotagmin) which intertwine to pull the vesicle towards the plasma membrane of the synaptic bulb.
• The vesicle fuses with the plasma membrane, releasing acetylcholine into the synaptic cleft.

Acetylcholine Production and Release

• Mitochondria produce Acetyl CoA
• Choline from the diet combines with Acetyl CoA to make Acetylcholine.
• Acetylcholine is transported into synaptic vesicles, using a proton pump to concentrate protons.
• Acetylcholine diffuses across the synaptic cleft and binds to nicotinic receptors (primarily type 1) on the muscle cell membrane.
• Binding opens the channels, allowing sodium to flow in and potassium to flow out.
• More sodium ions come in than potassium ions go out, producing a small depolarization called the end plate potential (EPP).
• The EPP moves along the membrane, opening voltage-gated sodium channels.

Voltage-Gated Sodium Channels

• Activation gates are stimulated by threshold potential (approximately -55 mV) and open quickly.
• Inactivation gates are also stimulated by threshold potential but close slowly.
• Sodium flushes in until the potential reaches approximately +30 mV., at which point the inactivation gate closes.
• Positive charges move along the muscle cell membrane and depolarize the T-tubules.

T-Tubules and Sarcoplasmic Reticulum

• T-tubules are invaginations of the sarcolemma (plasma membrane) and are coupled with the sarcoplasmic reticulum.
• A triad is formed by a T-tubule with sarcoplasmic reticulum on both sides.
• The action potential moving down the T-tubule stimulates the dihydropyridine receptor, which is mechanically coupled to the ryanodine receptor type 1 on the sarcoplasmic reticulum.
• This causes the ryanodine receptor to open, releasing calcium from the sarcoplasmic reticulum.

Calcium Concentration and Release

• Calcium is highly concentrated in the sarcoplasmic reticulum due to calsequestrin.
• When ryanodine receptors are displaced, calcium leaves the sarcoplasmic reticulum and enters the sarcoplasm (the fluid part of the muscle cell containing myofibrils and mitochondria).
• This occurs at the peak point of the action potential.

Myofilaments and Contraction

• Calcium binds to the troponin C site which pulls on troponin T, which is linked to tropomyosin. This binding unblocks the active sites on actin, allowing myosin heads to bind.
• Troponin has TNC, TNT, and TNI sites where calcium binds.
• Tropomyosin blocks myosin heads from binding to actin active sites when the muscle cell is at rest. Calcium stimulus allows contraction to begin.

Myosin-Actin Interaction

• ATP binds to the myosin head, causing it to detach from actin.
• ATP is hydrolyzed into ADP and inorganic phosphate, causing the myosin head to "cock" back into a high-energy position.
• The myosin head binds to actin, and the release of inorganic phosphate initiates the power stroke, pulling the actin filament towards the M-line.
• ADP is then released, leaving myosin in an uncomfortable position.
• ATP then binds to myosin, causing it to detach from actin and start the cycle again.
• Cellular respiration (aerobic and anaerobic) provides ATP for this process.

Sarcomere Changes During Contraction

• A-band: The length of the thick filament; stays the same during contraction.
• I-band: The distance from the end of one thick filament to the thick filament on the other sarcomere; decreases during contraction as the Z discs are pulled closer.
• H-zone: The distance between thin filaments; disappears during contraction as thin filaments slide over each other.
• Z discs: Get closer to one another during contraction.
• M-line: Where myosin filaments attach.

Role of Titan

• Titan is a very elastic protein that prevents overstretching and provides structural support to the sarcomere.
• During contraction, Titan gets stretched and pulls on Z discs, bringing them closer together.

Muscle Relaxation

• Muscle relaxation is equally important, and involves voltage-sensitive potassium channels, calcium channels, sodium-calcium exchanger proteins, and proteins on the sarcoplasmic reticulum.

Explanation of skeletal muscle contraction, detailing action potential transmission, the role of acetylcholine, and calcium release. Describes their coupling with contraction activity, from somatic motor neuron firing to membrane potential changes.