Muscle Contraction & Relaxation: Phases, Mechanisms, and Regulation

Four major phases of contraction and relaxation

Excitation, Excitation-contraction coupling, Contraction, Relaxation

Excitation

Action potentials in the motor nerve fiber lead to action potentials in the muscle fiber; action potential travels down the motor neuron's axon, reaches axon terminal, causes Ca2+ influx into the axon terminal from the extracellular fluid which then triggers exocytosis of ACh from the axon terminal into the neuromuscular junction; ACh diffuses across the synaptic cleft and binds onto the cholinergic receptors on the motor end plate, opening the ligand-gated Na+ ion channel and allowing Na+ influx into the muscle cell; an action potential is generated and it travels along the sarcolemma of the muscle cell

Excitation-contraction coupling

Events that link the action potentials on the sarcolemma to activation of the myofilaments, thereby preparing them to contract; the first step is the release of Ca2+ from the SR; the action potential that is traveling along the sarcolemma reaches a T tubule and is directed towards the interior of the muscle cell; the action potential reaches the terminal cisterns of the SR and causes the voltage-gated Ca2+ to open; Ca2+ then flows into the sarcoplasm; the released Ca2+ (from the SR) enter the sarcoplasm and can now bind onto troponin; binding of Ca2+ to troponin changes the shape of troponin which then shifts the tropomyosin filament so that it is no longer blocking the active sites (myosin binding sites) on F-actin

Contraction

The step in which the muscle fiber develops tension and may shorten; myosin in the high energy state/recovery stroke (it has ADP and Pi attached to the ATP binding site on the head of the myosin) can now bind onto the exposed active sites on F-actin; the myosin head binds onto the active site on F-actin forming a cross-bridge; the ADP and Pi leave the myosin head which causes the head to pivot and pull the F-actin closer to the M line, this is known as the power stroke which pulls the thin filament closer to the M line; ATP binds onto the ATP binding site on the myosin head causing it to detach from the active sites on F-actin, Note: the ATP binding site has ATPase activity which will break down ATP to ADP and Pi; the contraction cycle can keep going as long as there is Ca2+ in the sarcoplasm and ATP available to bind onto the ATP binding site on the myosin head; Note: during muscle relaxation and contraction, the Ca2+ pumps (active transporters that use ATP to move Ca2+ into the SR) are always working to keep the Ca2+ levels low in the sarcoplasm

Relaxation

When stimulation ends, a muscle fiber relaxes and returns to its resting length; AChE in the synaptic cleft breaks down the ACh released by the motor neuron; if there isn't enough ACh in the synaptic cleft, then the ligand-gated Na+ channels will close which stops the generation of action potential in the muscle and the closing of voltage-gated Ca2+ channels on the SR (since no AP at the T tubule); since the voltage-gated Ca2+ channels on the SR are now closed, the Ca2+ pumps on the SR can reduce the Ca2+ level in the sarcoplasm; now there isn't enough Ca2+ to bind to troponin and tropomyosin shifts and blocks the active sites on F-actin, preventing myosin from attaching to it; since there isn't enough Ca2+ to bind troponin, troponin shifts the tropomyosin strand and causes tropomyosin to re-block the active sites on F-actin which prevents myosin from attaching to it

Muscle Contraction/Relaxation

As the muscle fiber shortens, the sarcomere shortens and

the Z lines at each end of the sarcomere get closer to the M line; as sarcomeres shorten, muscle pulls together, producing tension; muscle shortening can occur at both ends of the muscle, or at only one end of the muscle, this depends on the way the muscle is attached at the ends, usually, a muscle is held fixed at the origin with the insertion end moving towards the fixed end during muscle contraction; muscle length returns to resting length passively; titin helps the sarcomere return back to the normal size

Tension Production by Muscles Fibers

As a whole, a muscle fiber is either contracted or relaxed; depends on: the number of pivoting cross-bridges that are formed, the fiber's resting length at the time of stimulation, the frequency of stimulation of the muscle cell

Length-tension relationship

The amount of tension generated by a muscle depends on how stretched or shortened it was before it was stimulated; if overly shortened before stimulated, contraction is weak and thick filaments butt up against Z discs, some thin filaments overlap; if too stretched before stimulated, contraction is weak and there is minimal overlap between thick and thin filaments results in minimal cross-bridge formation; optimum resting length produces greatest force when muscle contracts and nervous system maintains muscle tone (partial contraction) to ensure that resting muscles are near this length

The Frequency of Stimulation

A single neural stimulation produces a single contraction or twitch which lasts about 7-100 msec; sustained muscular contractions require many repeated stimuli from the motor neuron

Rigor Mortis

Hardening of muscles and stiffening of body beginning 3-4 hours after death; deteriorating sarcoplasmic reticulum releases Ca2+ and deteriorating sarcolemma allows Ca2+ to enter the sarcoplasm; the Ca2+ pumps do not have ATP to power it; Ca2+ activated the myosin-acting cross-bridge formation and muscle contraction occurs; muscle relaxation requires ATP, and since the cell is dead

and cannot produce new ATP after cell death, the muscle

stays contracted until the myofilaments begin to decay; rigor mortis peaks about 12 hours after death, then diminishes over the next 48-60 hours

Threshold

Minimum voltage that causes a muscle twitch; even if the same voltage is delivered, different stimuli cause twitches varying in strength, because: the muscle's starting length influences tension generation, muscles fatigue after continual use, warmer muscles' enzymes work more quickly, muscle cell's hydration level influences cross-bridge formation (affects the spacing between thick/thin

filaments), increasing the frequency of stimulus delivery increases tension output

Tension Production/Twitch Strength by Muscle Fiber

Treppe, Wave Summation, Frequency of stimulation

Treppe

A stair-step increase in twitch tension; repeated stimulations immediately after relaxation phase; stimulus frequency (50/second); causes a series of contractions with increasing tension; increase in tension caused by gradual increase in Ca2+ concentration in the sarcoplasm (Ca2+ pumps not fast enough to pump all of the previously released Ca2+ back into the SR)

Wave summation

Increasing tension or summation of twitches; repeated stimulations before the end of relaxation phase; stimulus frequency (50/second); causes increasing tension or summation of twitches

Frequency of stimulation

Low frequency stimuli produce identical twitches; higher frequency stimuli produce temporal (wave) summation, each new twitch "rides piggyback" on the previous one generating higher tension, only partial relaxation between stimuli resulting in fluttering, incomplete tetanus (the maximum tension fluctuates); unnaturally high stimulus frequencies (in lab experiments) cause a steady, contraction called complete (fused) tetanus (the maximum tension is a flat line)

Tetanus (disease)

The disease tetanus/"lockjaw" caused by toxin from

Clostridium tetani bacterium; the toxin causes over activity of skeletal muscle motor neurons (by blocking inhibitory interneurons in spinal cord); results in overstimulation of the muscle causing muscle stiffness, headaches, difficulty swallowing; vaccines: Tdap (tetanus, diphtheria, and pertussis) or Td (tetanus and diphtheria) for children over 7 and adults

Motor units in a skeletal muscle

Contain hundreds of muscle fibers that contract at the same time; these muscle fibers are all controlled by a single motor neuron

Stimulus Intensity and Contraction Strength

Muscles must contract with variable strength for different tasks; stimulating the nerve with higher voltages produces stronger contractions; higher voltages excite more nerve fibers which stimulate more motor units to contract; recruitment or multiple motor unit (MMU) summation; occurs according to the size principle - weak stimuli (low

voltage) recruit small units, while strong stimuli recruit

small and large units for powerful movements

Recruitment or multiple motor unit (MMU) summation

The process of bringing more motor units into play with

stronger stimuli

The Relationship Between Stimulus Intensity (Voltage) and Muscle Tension

Maximum tension can be generated when all motor units reach tetanus, however, this can only be sustained for a very brief amount of time

Motor Units and Tension Production

Sustained tension; less than maximum tension; allows motor units to rest in rotation

Muscle tone

The normal tension and firmness of a muscle at rest; muscle units actively maintain body position, without motion; increasing muscle tone increases metabolic energy used, even at rest

Different kinds of contraction

Isometric contraction, Isotonic contraction

Isometric contraction

Contraction without a change in length; muscle produces internal tension but external resistance causes it to stay the same length; can be a prelude to movement when tension is absorbed by elastic component of muscle; important in postural muscle function and antagonistic

muscle joint stabilization

Isotonic contraction

Contraction with a change in length but no change in tension; muscle changes in length with no change in tension; types: Concentric contraction, Eccentric contraction

Concentric contraction

Muscle shortens as it maintains tension (example: lifting weight)

Eccentric contraction

Muscle lengthens as it maintains tension (example: slowly lowering weight)

Forces that return muscles to their resting length

Muscle cannot actively return to their resting length; other forces involved during muscle relaxation: Elastic forces, Opposing muscle contractions, Gravity

Elastic forces

The pull of elastic elements (tendons and ligaments); expands the sarcomeres to resting length

Opposing muscle contractions

Reverse the direction of the original motion; are the work of opposing skeletal muscle pairs

Gravity

Can take the place of opposing muscle contraction to return a muscle to its resting state