Skeletal and Smooth Muscle Contraction

Skeletal Muscle Contraction: 1. Neural Activation: It starts with the arrival of an action potential at the axon terminal, neuromuscular junction (NMJ). 2. Release of Acetylcholine (ACh): In response to the action potential, the neuron releases the neurotransmitter ACh in...

Skeletal Muscle Contraction: 1. Neural Activation: It starts with the arrival of an action potential at the axon terminal, neuromuscular junction (NMJ). 2. Release of Acetylcholine (ACh): In response to the action potential, the neuron releases the neurotransmitter ACh into the synaptic cleft of the neuromuscular junction. 3. Depolarization of Muscle Fiber: ACh binds to receptors on the muscle cell's sarcolemma (nicotinic), causing sodium channels to open. Sodium ions rush into the muscle cell, leading to depolarization and generating an action potential on the muscle cell membrane (sarcolemma). 4. Spread of Action Potential: The action potential travels rapidly along the sarcolemma and down the T-tubules. 5. Activation the voltage-sensitive L-type calcium channels (also known as dihydropyridine receptors or DHPR) on the T-tubules. - The DHPR is mechanically coupled to the ryanodine receptor (RyR) on the sarcoplasmic reticulum (SR). - Activation of RyR leads to the release of Ca²⁺ from the SR into the sarcoplasm. 6. Release of Calcium from Sarcoplasmic Reticulum: The action potential triggers the release of Ca²⁺ ions from the sarcoplasmic reticulum into the muscle cell's cytoplasm. 7. Troponin-Tropomyosin Shift: The released Ca²⁺ ions bind to troponin, causing a conformational change that moves tropomyosin away from myosin-binding sites on actin filaments. 8. Cross-Bridge Formation: Myosin heads bind to the exposed sites on actin, forming cross-bridges. 9. Power Stroke: With the hydrolysis of ATP to ADP + Pi (inorganic phosphate), the myosin head pivots and pulls the actin filament towards the center of the sarcomere, causing muscle shortening and generating tension. 10. Release of ADP + Pi: Following the power stroke, ADP and Pi are released from the myosin head inducing the "rigor state" of cross bridge cycling. Skeletal Muscle Relaxation: 1. Termination of Neural Signal: The motor neuron stops releasing ACh. 2. Degradation of Acetylcholine: Acetylcholinesterase, an enzyme located in the synaptic cleft, breaks down ACh, ending the muscle stimulation.  3. Repolarization: With the end of the stimulation, potassium ions exit the muscle cell, leading to repolarization of the sarcolemma. 4. Active Transport of Calcium: Active transport pumps in the sarcoplasmic reticulum membrane pump Ca²⁺ ions back into the sarcoplasmic reticulum. 5. Return of Troponin-Tropomyosin Complex: As calcium ions are removed from troponin, tropomyosin returns to its original position, covering the myosin-binding sites on actin. 6. Detachment of Cross-Bridges: With the absence of Ca²⁺ and the repositioning of tropomyosin, myosin heads detach from actin, and cross-bridges are broken. 7. Muscle Relaxation: The muscle fiber returns to its resting state. Smooth Muscle Contraction: 1. Stimulus: The smooth muscle cell can be stimulated by various factors, including neurotransmitters (like norepinephrine), hormones (like oxytocin), and more! GPCR signaling activated by neurotransmitters and/or hormones, results in the activation of multiple signaling cascades involving: PLC and Rho-kinase PLC activation leads to the signaling of both IP3 and DAG IP3 binds the IP3 gated Ca²⁺ channel on the SR leading to an increase in intracellular calcium (see step "2" next) DAG activates PKC, activating CPI-17, leading to the inhibition of MLCP Rho-kinase activation leads to the inhibition of MLCP 2. Influx of Calcium: The stimulus leads to an influx of extracellular Ca²⁺ ions through voltage-dependent or receptor-operated calcium channels. 3. Calcium Binds to Calmodulin: The increased intracellular Ca²⁺ binds to the protein calmodulin, forming a Ca²⁺-calmodulin (Ca²⁺-CaM) complex. 4. Activation of MLCK: The Ca²⁺-calmodulin complex activates myosin light chain kinase (MLCK). Additionally, Ca²⁺-CaM inhibits the two actin bound myosin ATPase inhibitors (calponin and caldesmon). By inhibiting calponin and caldesmon it allows for the myosin head to experience appropriate ATP hydrolysis promoting cross bridge cycling. 5. Phosphorylation of Myosin: MLCK then phosphorylates the light chain of myosin molecules, enabling the myosin heads to interact with actin filaments.  6. Cross-Bridge Formation: The phosphorylated myosin heads bind to actin, forming cross-bridges. 7. Power Stroke: Using energy from ATP hydrolysis, the myosin heads undergo a conformational change, pulling the actin filaments inwards. This leads to muscle contraction. 8. Sustained Contraction: Smooth muscle can sustain contraction with little energy expenditure by latching the myosin heads onto actin, maintaining tension. Smooth Muscle Relaxation: 1. Removal of Stimulus: The initial stimulus (e.g., neurotransmitter or hormone) is removed or reduced. 2. Calcium Pump Activation: Active transport mechanisms, primarily SERCA pump, push Ca²⁺ ions out of the cell and back into the sarcoplasmic reticulum. 3. Decrease in Intracellular Calcium: As intracellular Ca²⁺ levels decrease, calcium unbinds from calmodulin. 4. Dephosphorylation of Myosin: Myosin phosphatase (MLCP) dephosphorylates the light chain of myosin, reducing its affinity for actin. 5. Cross-Bridge Detachment: As myosin is dephosphorylated, myosin-actin cross-bridges detach. 6. Muscle Relaxation: With fewer active cross-bridges, tension in the muscle decreases, leading to muscle relaxation.