Muscle Tissue
The Neuromuscular Synapse
Synapse: Site of communication between a neuron and another cell.
Muscle cell = neuromuscular junction
Gland = neuroglandular junction
The Neuromuscular Junction Terminology
For skeletal muscle, the neuromuscular synapse is also referred to as:
Neuromuscular junction
Motor end-plate
Action Potential at the Neuromuscular Junction
An action potential from a neuron creates an action potential in a muscle cell at the neuromuscular junction.
Key components and processes include:
Nerve impulse
Voltage-gated Ca^{2+} channels
Release of Acetylcholine (ACh)
v-SNARE proteins
Motor terminal axon
Nicotinic ACh receptors
Acetylcholinesterase (AChE)
Sarcolemma
T-tubule
Sarcoplasmic reticulum
Dihydropyridine (DHP) receptors
Ryanodine receptors (RYR)
SERCA pumps
Changes in Membrane Potential
Resting Membrane Potential
Depolarization: Membrane potential becomes less negative (more positive).
Repolarization: Membrane potential returns to resting value.
Hyperpolarization: Membrane potential becomes more negative.
Excitation-Contraction Coupling in Skeletal Muscle
Excitation-Contraction Coupling: How the action potential from a motor neuron causes muscle contraction.
Release of acetylcholine at the neuromuscular junction causes an electrical impulse to be generated in the muscle cell plasma membrane.
The electrical impulse is carried to the cell's interior by the T tubules.
The electrical impulse triggers the release of Ca^{2+} from the sarcoplasmic reticulum.
Ca^{2+} Release from the Terminal Cisternae
Muscle action potential is propagated.
In the lumen of the T-tubule (extracellular space):
Voltage-sensitive protein is polarized.
T-tubule membrane.
In the cytosol:
Sarcoplasmic reticulum membrane.
Ca^{2+} release channel.
In the lumen of the sarcoplasmic reticulum:
Dihydropyridine (DHP) receptor
Ryanodine receptor
Ca^{2+} released from terminal cisternae.
Ca^{2+} binding to troponin removes the blocking action of tropomyosin.
Cross-bridge moves.
Ca^{2+} taken up.
Ca^{2+} removal from troponin restores tropomyosin blocking action.
Regulation of Striated Muscle Contraction by Ca^{2+}
When Ca^{2+} binds to troponin, the troponin complex pulls tropomyosin off the myosin-binding sites.
Excitation-Contraction Coupling in Striated Muscle
In resting muscle, the sarcoplasmic Ca^{2+} concentration is very low.
In resting muscle, tropomyosin blocks the myosin-binding sites on the actin thin filaments.
Following the action potential, the cytosolic Ca^{2+} concentration increases.
The Ca^{2+} binds to troponin, causing the troponin complex to change its shape and pull tropomyosin out of the way.
The myosin-binding sites are now exposed, allowing actin and myosin to interact.
Later, when the Ca^{2+} is pumped back into the sarcoplasmic reticulum, the Ca^{2+} comes off troponin, and the troponin shape changes back, pulling tropomyosin back over the myosin-binding sites. This stops contraction.
Contraction Cycle
Contraction Cycle Begins: The contraction cycle involves a series of interrelated steps, beginning with the arrival of calcium ions (Ca^{2+}) within the zone of overlap in a sarcomere.
Active-Site Exposure: Calcium ions bind to troponin, weakening the bond between actin and the troponin-tropomyosin complex. The troponin molecule then changes position, rolling the tropomyosin molecule away from the active sites on actin and allowing interaction with the energized myosin heads.
Cross-Bridge Formation: Once the active sites are exposed, the energized myosin heads bind to them, forming cross-bridges.
Myosin Head Pivoting: After cross-bridge formation, the energy that was stored in the resting state is released as the myosin head pivots toward the M line. This action is called the power stroke; when it occurs, the bound ADP and phosphate group are released.
Cross-Bridge Detachment: When another ATP binds to the myosin head, the link between the myosin head and the active site on the actin molecule is broken. The active site is now exposed and able to form another cross-bridge.
Myosin Reactivation: Myosin reactivation occurs when the free myosin head splits ATP into ADP and P. The energy released is used to recock the myosin head.
Relaxation of a Muscle
Three factors that determine the length of a muscle contraction:
Length of stimulation at the neuromuscular junction
Acetylcholine (Ach) is cleared from the synaptic cleft via:
Diffusion out of the synaptic cleft
Acetylcholinesterase – enzyme that breaks down Ach
Ach à acetate + choline
Choline is taken back up into the neuron and recycled to make more Ach
The presence of Ca^{2+} in the sarcoplasm
Active transport of Ca^{2+} via Ca^{2+} pumps
Into the sarcoplasmic reticulum (recycles Ca^{2+})
Across the sarcolemma into the interstitial fluid
The availability of ATP
Steps in the Initiation and Termination of a Contraction
The electrical impulse is initiated.
Action potential reaches T-tubule.
Sarcoplasmic reticulum releases Ca^{2+}.
Active-site exposure, cross-bridge binding.
Contraction begins.
The electrical impulse is terminated.
Sarcoplasmic reticulum recaptures Ca^{2+}.
Active sites covered, no cross-bridge interaction.
Contraction ends.
Relaxation occurs, passive return to resting length.
Skeletal Muscle Motor Units
Motor unit: Consists of a single motor neuron and all the muscle fibers it innervates.
Range in size from 1:3 (fine control) to 1:1000 (leg muscles).
Each muscle fiber controlled by a motor unit:
Is innervated only once
Contracts simultaneously
Recruitment: Smooth and steady increase in muscle tension resulting from increasing the number of active motor units.
Regulation of Muscle Tension
The force generated by a skeletal muscle depends on the number of muscle fibers stimulated and the frequency of stimulation.
Skeletal muscle contraction begins with a small number of motor units.
If more force is needed, the CNS will recruit additional motor units.
Muscle Twitch
Twitch: A single neural stimulation produces (lasts ~ 7-100 msec.)
Latent period
The action potential moves through sarcolemma
Causing Ca^{2+} release
Contraction phase
Calcium ions bind
Tension builds to peak
Relaxation phase
Ca^{2+} levels fall
Active sites are covered, and tension falls to resting levels
Sustained muscular contractions require many repeated stimuli
Muscle Twitches and Skeletal Muscle Fiber Types
Three Types of Muscle Fibers
Fast fibers
Reach peak tension in 0.01 second or less
Densely packed myofibrils
Few mitochondria
Large glycogen reserves
Supported by anaerobic metabolism
Slow fibers
Take 3x longer to reach peak tension than fast fibers
½ the diameter
Numerous mitochondria
Surrounded by numerous capillaries (to deliver O2)
Contain a red pigment called myoglobin (similar to hemoglobin) – binds O2
Supported by aerobic metabolism
Intermediate fibers
More similar in appearance to fast fibers (pale, scant myoglobin)
More resistant to fatigue than fast fibers (intermediate capillary network & mitochondria)
Most skeletal muscles have a mix of all 3 fiber types.
Fast motor units - rapidly fatiguing, white muscle fibers; short bursts of action potentials from motor neuron
Slow motor units - slowly fatiguing, red muscle fibers; slow, steady firing of action potential from motor neuron
Effects of Repeated Stimulations on Muscle Tension
Wave summation
Repeated stimulations before the end of relaxation phase
Stimulus frequency >50/second
Causes increasing tension or summation of twitches
Incomplete tetanus
Continuing rapid stimulation
Periods of relaxation are brief
Twitches reach maximum level of tension
Complete tetanus
High stimulation frequency
Muscle never begins to relax
Muscle is in continuous contraction
Tetanus (disease) – aka “Lockjaw”
Clostridium tetani
Anaerobic bacterium
Produces a toxin that inhibits the release of inhibitory neurotransmitters
40-60% mortality rate
~100 in the US (due to immunizations)
Rigor Mortis
A fixed muscular contraction after death
Causes: ATP is no longer available
Active transport mechanisms don’t work (Na^+/K^+ and Ca^{2+} pumps)
Ion pumps no longer function -> Ca^{2+} builds up in the sarcoplasm
Cross-bridges unable to detach
Begins 2-7 hours after death
Lasts between 1-7 days
Ends when lysosomal enzymes break down Z-lines and titin proteins
Skeletal Muscle Tone
Resting tension in a skeletal muscle
Purpose:
Keeps muscle ready to respond
Helps stabilize joints and maintain posture
Different fibers contract at different times to provide muscle tone.
Muscle tone is maintained by involuntary spinal reflexes responding to stretch receptors in the muscle and tendons.
Increasing muscle tone increases metabolic energy used, even at rest
Factors that Affect Tension Production
Tension Production by Muscles Fibers Depends on:
The fiber’s resting length at the time of stimulation (sarcomere length at rest)
The amount of overlap between myosin and actin
The frequency of stimulation
Factors That Affect Tension Production: Sarcomere Length
At short resting lengths, thin filaments extending across the center of the sarcomere interfere with the normal orientation of thick and thin filaments, decreasing tension production.
Maximum tension is produced when the zone of overlap is large but the thin filaments do not extend across the sarcomere's center.
If the sarcomeres are stretched too far, the zone of overlap is reduced or disappears, and cross-bridge interactions are reduced or cannot occur.
When the thick filaments contact the Z lines, the sarcomere cannot shorten—the myosin heads cannot pivot and tension cannot be produced.
Optimal resting length: The normal range of sarcomere lengths in the body is 75 to 130 percent of the optimal length.
When the zone of overlap is reduced to zero, thin and thick filaments cannot interact at all. The muscle fiber cannot produce any active tension, and a contraction cannot occur. Such extreme stretching of a muscle fiber is normally prevented by titin filaments (which tie the thick filaments to the Z lines) and by the surrounding connective tissues.
Types of Muscle Contractions
Contractions are classified based on pattern of tension production
Isotonic contraction – skeletal muscle changes length resulting in motion
If muscle tension > load (resistance):
Muscle shortens (concentric contraction)
What we envision when we think about muscle contraction
If muscle tension < load (resistance):
Muscle lengthens (eccentric contraction)
Tip to remember: eccentric means ”unconventional” or “somewhat strange”
Isometric contraction – skeletal muscle length remains the same
Muscle maintains position (doesn’t move) but contraction is initiated
Types of Skeletal Muscle Contractions
Isometric contraction – contraction of the muscle without the muscle shortening or lengthening
muscle tension = load (resistance)
Concentric contraction – contraction of the muscle results in the shortening of the muscle
muscle tension > load (resistance):
Eccentric contraction – muscle is contracted but its force is less than the load resulting in the lengthening of the muscle
muscle tension < load (resistance)
Cardiac Muscle
Cardiac muscle cells (cardiomyocytes) differ from skeletal muscle fibers in several ways:
Cardiac muscle cells are smaller
Have only 1 nucleus
Cardiac muscle cells are joined by gap junctions.
Some cardiac cells are autorhythmic – initiate their own action potentials (cardiac pacemaker cells)
Smooth Muscle
Involuntary – no conscious control
Spindle-shaped cells
Single nucleus
Has no striations (no sarcomeres)
Transfer action potentials via gap junctions
Usually organized into sheets/layers
Exhibits slow, prolonged contraction with low energy requirements
Found in the walls of blood vessels and hollow organs of the respiratory, digestive, urinary, and reproductive tracts
Smooth Muscle Contraction
Note: The thin filaments are much longer in smooth muscle cells.
Consequently, the range of lengths over which a smooth muscle cell can develop near maximal tension is much greater than for a skeletal muscle.
Smooth muscle can still develop considerable tension even when stretched up to 2.5× its resting length.
Consequently, the hollow organs of the respiratory, digestive, urinary, and reproductive tracts can accommodate large volumes but can empty to practically zero volume.