PSL300 - Skeletal Muscle Overview

PSL300 - Muscle

• PSL300 is a physiology course at the University of Toronto.
• The course covers skeletal muscle, smooth muscle, and cardiac muscle.

Skeletal Muscle

• Activated by the somatic nervous system

• Motor neurons and associated muscle fibers form a motor unit.

• Chemical signaling between motor neurons and skeletal muscle forms a neuro-muscular junction (NMJ)

• NMJ = the synapse between the motor neuron and muscle fiber

• Axon terminals of motor neurons.

• Muscle fibers are striated, with contractile filaments in sarcomeres

• Well-developed sarcoplasmic reticulum (SR)

• Muscle = group of fascicles, muscle fibers extend from tendon to tendon

• Skeletal muscle consists of muscle fibers that are further subdivided into fascicles

• Fascicles are bundles of muscle fibers, covered by connective tissues.

• Muscle fibers are made up of myofibrils

• Sarcolemma = plasma membrane, T-tubules are invaginations of the sarcolemma into the muscle fiber

• Sarcoplasmic reticulum = intracellular organelle, storage for Ca++

• Thick filaments are made up of myosin

• Thin filaments are made up of actin

Motor Unit

• A motor unit consists of one motor neuron and all the muscle fibers it innervates.
• The muscle fibers of a motor unit contract together.
• The smoothness and precision of movement depend on the number and timing of active motor units
• Muscle contraction begins with small motor units being activated first.
• All muscle fibers in a motor unit are the same type.
• There are three broad categories of muscle fibers (e.g., slow oxidative, fast oxidative-glycolytic, fast glycolytic), which are based on histochemical characteristics.

Muscle Fiber Types

• Slow-twitch oxidative fibers: Slowly contracting, many mitochondria, oxidative metabolism.

• Fast-twitch oxidative-glycolytic fibers: Intermediate speed, oxidative and glycolytic, moderate fatigue resistance

• Fast-twitch glycolytic fibers: Fast twitch time, produce large tension, rapid fatigability, glycolytic metabolism.

• Small diameter motor neurons innervate slow oxidative fibers

• Large diameter motor neurons innervate fast glycolytic fibers

• Small diameter motor neurons are more easily excited than large diameter motor neurons.

Properties of NMJ

• Anatomy of the neuromuscular junction: Terminal bouton = axon terminal (motor neuron), Motor end plate = specialized muscle membrane at the junction.
• All motor neurons release acetylcholine.
• All synapses are excitatory.
• Activation of motor neurons depends on summation of EPSPs/IPSPs

Communication at the NMJ

• Action potential arrives at terminal bouton
• Voltage-gated calcium channels open
• Calcium enters cell, triggering release of acetylcholine (ACh)
• ACh diffuses across cleft and binds to nicotinic receptors on motor end plate
• ACh binding triggers opening of channels for small cations (Na and K)
• There is a net movement of positive charge into the muscle fiber > depolarization
• This causes an action potential in the muscle cell
• Action potential spreads through muscle, causing contraction

Poisoning the NMJ

• The brain is protected from toxins in the blood by the blood-brain barrier.

• Peripheral tissues (e.g., muscle) are exposed to circulating toxins, which can block the NMJ.

• Toxins that block the NMJ fall into three types: nicotinic receptor blockers (e.g., poison darts, curariform drugs, botox), exocytosis blockers, and ACh-esterase inhibitors (e.g., nerve gases, pesticides).

Mechanism of Force Generation

• The crossbridge cycle describes how muscles generate force.

Skeletal Muscle Fiber

• Thin filaments are made up of actin.
• Thick filaments are made up of myosin.

Structure of a Sarcomere

• Actin and myosin are organized in an overlapping arrangement.
• Muscle contraction = sarcomere shortening.
• Actin and myosin do not change length, but slide past one another.

Thick Myofilament

• Thick filament is made up of myosin molecules.
• Myosin head contains actin binding site and ATP binding site

Thin Myofilament

• Thin filament is made up of two strands of actin molecules.
• Actin molecules have a binding site for myosin.

Troponin & Tropomyosin Actions

• No Calcium: troponin holds tropomyosin over myosin binding sites on actin.
• No crossbridges form between actin and myosin. Muscle relaxed.
• Calcium present: binds to troponin causing movement of tropomyosin, exposing binding sites for myosin on actin. Crossbridges form between actin and myosin, muscle contracts.

Crossbridge Cycle

• Myosin head undergoes conformation changes swiveling back-and-forth.
• High-energy form - high affinity for actin
• Low-energy form - low affinity for actin-
• Relies on ATP hydrolysis
• Power stroke: Myosin head moves propelling thin filament towards center of muscle via ATP hydrolysis
• Thick and thin filaments detach
• Myosin head returns to initial position, cycle starts again.

Cardiac Muscle

• Contractile cells and conductile cells
• Intermediate development of SR
• Gap junctions for synchronous beat
• Activity modulated by ANS (unlike skeletal muscle—somatic nervous system)

Cardiac Muscle - AP

• AP duration 300ms in ventricles
• AP plateau due to slow Ca2+ channels allows time for forceful contraction from a single AP.
• Plateau allows muscle contraction to last 300ms (20-50x longer than in skeletal muscle)
• AP shape and duration reflect changing permeability to Na+, Ca2+
• Cardiac contractile cell APs last almost as long as contraction/relaxation

Cardiac Muscle Contraction

• One way to increase force of contraction is via increasing muscle length, known as the Starling law.
• Other ways to increase force of contraction include increasing motor unit recruitment and excitation/contraction coupling

Excitation-Contraction Coupling

• Lacks specialized receptor regions
• Ca2+ is from the extracellular fluid and sarcoplasmic reticulum
• Ca2+ initiates a cascade ending with the phosphorylation of myosin light chain and activation of myosin ATPase
• Opening of calcium channels in plasma membrane
• Calcium triggers release of calcium from sarcoplasmic reticulum
• Calcium binds to calmodulin
• Ca-Calmodulin activates MLCK
• MLCK phosphorylates myosin
• Crossbridge cycling

Relaxation of Smooth Muscle

• Phosphatase removes phosphate from myosin
• Calcium removed from cytoplasm
• Ca-ATPase
• Ca-Na counter transport

Twitch Contraction

• 3 phases of muscle twitch
• Latent period
• Period of contraction
• Period of relaxation

Summation and Tetanus

• In skeletal muscle, with increased AP frequency, successive twitches fuse with each other.
• Contractile force rises.
• Repeated stimulation fuses into a continuous contraction called tetanus.
• Summation leading to unfused tetanus—stimuli are far enough apart to allow muscle to relax slightly between stimuli
• Summation leading to complete tetanus—muscle reaches steady tension

Smooth Muscle

• Found in internal organs, blood vessels, and examples including vasculature, gastrointestinal tracts, urinary, reproductive, and respiratory tracts; pupil etc...

• Not arranged in sarcomeres

• Under involuntary control by ANS

• Must operate over a range of lengths

• Layers may run in several directions

• Contracts and relaxes much more slowly

• Uses less energy

Classification of Smooth Muscle

• By location (e.g., vascular, gastrointestinal, urinary, respiratory, reproductive, ocular)
• By communication with neighboring cells (e.g., single-unit/visceral smooth muscle, multi-unit smooth muscle)

Single-Unit Smooth Muscle

• Single-unit smooth muscles are connected by gap junctions and contract as a single unit
• Found in the intestinal tract, blood vessels, etc...
• Exhibits spontaneous activity, also activated by ANS.
• Able to actively exert tension in absence of external stimulation

Multi-Unit Smooth Muscle

• Multi-unit smooth muscle cells are not electrically linked and each cell must be stimulated independently
• Found in large airways, arteries, etc...
• Each fiber acts individually.
• Heavily innervated
• Generally, contracts only when nervous supply is stimulated.

This quiz tests your knowledge on skeletal muscle physiology as part of the PSL300 course at the University of Toronto. You'll explore concepts such as motor units, neuromuscular junctions, and the structural organization of muscle fibers. Perfect for those looking to strengthen their understanding of muscle anatomy and function.