Introduction to Human Physiology - 3 Muscle

Source: My personal notes from Introduction to Human Physiology | Coursera

In this module, we consider the effectors of the body that govern voluntary and involuntary movement. These effectors are specialized cells called muscle which are capable of generating force (tension). Muscle cells are classified as one of three types: skeletal, smooth, and cardiac. Although all three types generate tension, each is specialized for a given function. Skeletal muscle governs voluntary movement of the limbs and is critical for expansion of the lung during breathing. Smooth and cardiac muscle are contractile cells found in the walls of blood vessels and the heart, respectively. We will return to the basic principles that govern these cells types when we consider the respiratory and cardiovascular systems.

Muscle

Light microscope image of skeletle muscle, notice strips

Muscle types

• Nuclei are visible in these microscope images

• Skeletal muscles are striated. Muscle cells (aka fibres) are large in diameter and maybe length since they run the length of a muscle. The muscle cells will be multiple nuclei (they have more than one nuclei) and nuclei are usually at edges. Controlled by somatic NS

• Cardiac are also striated, small and contain 1-2 nuclei, connected by specialized junctions. Controlled by Autonomic NS

• Smooth muscle is present in many organs. They are not striated and have junctions. Controlled by Autonomic NS

Shared Principles of skeletal, cardiac, smooth muscle types

• The sliding filament mechanism, in which myosin filaments bind to and move actin filaments, is the basis for shortening of stimulated muscle.

• Myosin and actin interactions are regulated by calcium ions.

• Changes in the membrane potential lead to contraction; cell E-C coupling (excitation-contraction coupling)

 

Skeletal muscle cross section and zoomed in layers

• Skeletal muscle has many - muscle cells/fibers which has many - myobrils

• Myobrils are divided into sarcomeres in series. Number of myobrils determine force generation capability.

• Sarcomere patterns cause the striations.

 

Electron micrograph of a single Sarcomere Structure

Part of a myofibril  

• Sarcomeres have a light and dark pattern.

• Z lines are ends of sarcomeres

• Thin filaments are actin

• Thick filaments are myosin. Note myosin is surrounding the centre of the sarcomere. Myosin moves along the actin towards the Z lines. This movement like walking moves the myosin and actin together.

• A band (think dark has letter “A”) = thick colour (myosin is thick)

• I (eye) band (think light has the letter “I”) = light colour (actin)

 

• Relaxed -> Contracted : I band is reduced in width in contraction while A band is staying the same.

• Sarcomere becomes shorter.

• A band is the length of the myosin (red) and I band disappears since myosin and actin are together. The amount of actin that is alone is minimal in a contracted muscle.

 

Regulation by Calcium

How is the contraction occurring through Calcium?

 

• Top of diagram is actin

• Tropomyosin is parallel to actin. Without Ca, tropomyosin prevents actin and myosin from binding

• Troponin with Ca, allows myosin to bind with actin.

• Bottom of diagram shows myosin/actin binding

 

Cross Bridge Cycling

 

• Actin and myosin are bound.

• Myosin provides ATPase

• Rigor state is when myosin is tightly bound to actin with no ATP.

  • Examaple: It is the same state a dead person would be in since all ATP is quickly used up (rigor mortis). Eventually proteins of the muscle will break down removing the rigor state.

• ATP causes the myosin head to walk up closer to the Z line along the actin.

  • Myosin head lets go of actin and ratchets forward, and phosphates are released causing a “power stroke”.

  • ATP is released

• Return rigor state. Cycle continues.

• Why doesn’t the myosin slip back to a relaxed state when the head let’s go? there are many myosin heads in the muscle and they will be in different stages, so other heads will be in myosin-actin bound states during muscle contraction.

 

What is needed for contraction?

• Calcium

• ATP

 

Linking Somatic NS to Muscle contraction - Excitation-Contraction (E-C) Coupling

 

1. Somatic neuron sends a branch of the axon to synapse on skeletal muscle.

2. Neuron releases ACh given a graded potential. Ach will bind nicotinic ACh receptors on skeletal muscle plasma membrane

3. Na+ will enter membrane = graded potential. Small graded potential will cause an action potential since there are many Na+, K+ voltage gate channels on the membrane.

4. Action potentials will travel all over muscle membrane and across transverse (T) tubules that transfer the action potential into the muscle. Transverse = perpendicular to membrane.

5. Sarcoplasmic reticulum (S.R.) is close to T tubules. Inside the T-tubule is a voltage gate Ca channel called the dihydropyridine receptor. The change in the dihydropyridine receptor, changes the ryanodine receptor in the S.R. The proteins trigger a release of Ca++ in the cytosol.

6. Ca++ in cytosol binds the Troponin triggering myocin and actin binding (tropomyocin is removed).

7. Sarcoplasmic reticulum (S.R.) - Ca+ ATPase (aka SERCA) pumps Ca++ back into the S.R. So Ca++ is immediately pumped back in to the S.R. to prepare for future relaxation.

 

Myofibrils = grey

T Tubule = yellow, they go into the muscle cells, allowing E-C coupling coordination

Muscle plasma membrane = top yellow

Sarcoplasmic reticulum (S.R.) = blue, wraps around T tubules and myofibrils. With E-C coupling, myofibrils are bathed in Ca from S.R. S.R. can then retake Ca after contraction.

 

Key Concepts

All muscles are composed of two sets of overlapping protein filaments, actin and myosin. The relative sliding of which produce shortening and generates force. This process involves cross bridge formation between actin and myosin and uses ATP.

 

Couple between the membrane action potentials and contraction is mediated by calcium ions. Skeletal muscle has an actin-based (thin filament) control system. Relaxation occurs with the removal of Ca++.

 

Skeletal Muscle - Tension and Metabolism

Stimulus Frequency and Tension

 

• AP = action potential

• A twitch is due to a single action potential.

• Ca spikes in cytosol with action potential as it travels the muscle membrane.

• ATPase starts to remove Ca from S.R.

• A single action potential causes a single twitch, though tension will be small.

• AP duration = 5 milliseconds

• Twitch duration = 100 msec

 

More APs in a row will increase tension by resulting in myocin heads are walking up actin and increasing tension. Ca levels in cytosol will spike removing tropomyocin. This process is different in skeletal muscle and cardiac muscle.

 

Velocity of Shortening

Shortening Contractions (concentric contraction): For small loads, tension can remain consistent while muscle shortens for force generation, (e.g. lift small weights). Isotonic contraction means force generation by changing length of the muscle only and not tension.

Isometric contractions (maximal load): tension = load

Lengthening contraction (eccentric contraction): Load > Tension - you are releasing an object due to its weight or slowing down relaxation of muscles (e.g. sitting down in a chair with respect to quadriceps)

 

High velocities are possible with high tension and low loads. The greater the load, the lower the possible velocity of shortening.

 

 

Length - Tension Relationship

Looking at a sarcomere length in resting muscle:

• When sarcomere are too short-contracted (myocin near Z lines and right up against Z lines) or too long-stretched (heads of myocin too far away from actin to bind), then % of maximum force is low.

• Good force production is when myocin heads are near actin and have a distance to travel to the Z-lines to allow muscle contraction and force production (top of diagram where sarcomere are in an in-between length).

• Usually human skeleton will constrain the sarcomere lengths to these idea sarcomere lengths.

 

 

Metabolism and Fuels

What is the source of the ATP?

• ATP is necessary for Ca cycling in muscle.

• Creatine phosphate donates a phosphate to convert ADP to ATP in the first seconds of muscle activity, like 100 meter dash. Otherwise Creatine phosphate is exhausted

• Anaerobic metabolism (glycolytic) produces ATP and lactid acid using glycolysis. Burns glucose and muscle glycogen, like 400 meter dash.

• Aerobic metabolism (oxidate = requires oxygen) produces ATP, CO2, and water using oxidative phosphorylation, burns blood glucose, fatty acids, like marathon. Can be unlimited store of energy. Low ATP production/min.

 

Fuel sources: Glucose, glycogen, fatty acids

 

	Moles of ATP made/min	time	Running example
Creatine phosphate	4	8-10s	100m sprint
Anearobic	2.5	1.5 minutes	400m run
Aerobic	1	unlimited	marathon

 

Since the body has a lot of fat, aerobic metabolism can last a long time.

 

Fatigue State

 

Contributing factors include:

• Build up of ECF [K+] = persistent depolarization of fiber.

  • Not of enough time to get gradient back to resting state. Resting membrane potential will be less negative and less sensitive to neural stimulation as action potentials (AP) are harder to activate.

• Build up of metabolites which impair SR Ca2+ ATPase and troponin-tropomyosin

  • Muscle can’t be relaxes as Ca can’t be moved into SR

  • Muscle isn’t as responsive with troponin-tropomyosin

• Build up of Pi in ICF inhibits cross bridge detachment and slows cross bridge cycling

  • Building of inorganic phosphate (Pi) reduced ability of muscle to contract quickly.

• Decrease in fuel stores (glycogen, fatty acids, and glucose). This factor is usually not the cause of fatigue. Think about it. If fuel is completely used up, muscle would go into a rigor state (contracted) resulting in muscle damage. Myocin is locked down in actin while muscle is trying to be used. Fatigue protects the muscle from this state and muscle damage.

 

Fiber types and metabolism

 

Fiber type	ATP production speed	Power Generation	Fatigue Resistance	Example
Slow-oxidative	Low	Low	Good	Muscles for posture
Fast oxidative-glycolytic   Use a combination of oxidative and glycolytic ATP production	Medium	Medium	Ok	Walking muscles
Fast-glycolytic	High	High	Poor	Muscles for jumping

Fiber Types and Motor Units

Most skeletal muscles include all 3 fiber types

 

• Fiber types synapse with specific motor neuron. e.g. slow-oxidative neuron synapses with slow-oxidative fiber

• Each motor unit has one type of muscle fiber

• Small motor unit #1 has fewer fibers = finer movement

• Large motor unit #2 has more fibers = more tension

• Each fascicle contains more than one motor unit.

 

 

Recruitment

You want to do a movement. How is it initiated?

1. Slow-oxidative recruited first for movement = low force but high precision and/or long duration

2. Fast-oxidative-glycolytic recruited next = intermediate force

3. Fast-glycolytic recruited last = high force tasks of short duration

 

Recruitments can increase, depending on neurons recruited:

• number of fibers

• Force of fibers

 

 

Muscle Plasticity

Weight training induce hypertrophy to generate more tension (force).

• Size of muscles are increased, more myofibrils are created.

 

Endurance training induces resistance to fatigue without dramatic hypertrophy.

• Increases ability to use oxygen

• More capillaries in muscles and mitochondria in oxidative fibres.

 

Training changes relative size of fibers, not number of fibers. You are born with a certain type of fibre.

 

Key Concepts

Muscles can shorten at a constant force (isotonic contraction) or develop force without shortening (isometric contraction). Maximal velocity of shortening occurs with zero load. Summation of contractions (tetanus) can occur in skeletal muscle resulting in maximal force. Speed of contraction is set by the myosin ATPase.

 

The immediate fuel for muscle contraction is ATP which is generated under aerobic and anaerobic conditions. Those muscles with high requirements for ATP and resistance to fatigue have predominately aerobic metabolism.

 

Smooth Muscle

• Involuntary muscles

• Walls of organs and surrounds blood vessels

 

Shared Principles of Muscles

• Sliding filament mechanism (myosin-actin)

• Regulated by calcium

• Internal Ca++ cell leads to contraction

 

Smooth muscle fiber

 

2-20um , thin cell

Called smooth muscle since there isn’t much AI banding visible.

When contracted, cell looks like a square

 

Ca++ Regulates Myosin

Increase of intracellular [Ca++] -> Ca++ activates myosin light chain (MLC) kinase -> cross bridges formation (contraction coming) > contraction with shortening and tension in muscle.

 

Ca++ stored in sacroplasmic reticulum inside cell

 

To initiate relaxation in the cardiac myocyte, Ca++ is removed from the cytoplasm by:

• Sarcoplasmic reticulum Ca ATPase

• Plasma membrance Ca ATPase

• Plasma membrane Na-Ca exchanger

 

Types of Contraction

Slow myosin ATPase = slow contraction (difference in smooth muscle)

 

Tonic = amount of tension generation is proportional to the stimulus and sustained over time (e.g. muscles around blood vessels)

Phasic = single contraction followed by relaxation = twitch. Fused tetanus = tension is phasic

 

Regulation of Contraction

1. Mechanically gated channels (stretched walls of muscles) - e.g. blood vessels stretched, bringing Ca+

2. Ligand gate channels (chemical) or receptors

• Autonomic nervous system (NorEPI binding to receptors alpha 1, beta 2)

  • e.g. During an asthma attack, constriction of the bronchiolar smooth muscle restricts airflow into and out of the lung. Epinephrine is administered to restore air flow. Epinephrine binds to beta-2 adrenergic receptor, allowing brochi relaxation

• Hormones (e.g. Oxytocin)

• Paracrine agents (e.g. K+, H+)

3. Voltage gated channels

• Spontaneous pacemaker potentials

 

Pacemaker Activity

Packemakers have an unstable resting potential for their uniqueness.

Ca++ voltage channels are open and cause membrane potential to vary

Timed event = periodicity to potential changes

K+ channels are open, resulting in repolarization of the cell (as K leaves the cell, making the membrane potential negative.

 

Single Unit & Multi Unit Fibers (non-pacemaker smooth muscle)

 

In single-unit muscles: Certain cells are innervated. Whole sheet is synchronized. Gap junctions spread the membrane potentials between neightbouring cells.

(e.g. GI tract, uterus, and small blood vessels like arterioles)

 

In multi-unit muscle: each fiber is innervated. There are few or no gap junctions. These cells are not activated by stretch receptors (e.g. hair follicles)

 

Key Concepts

• Smooth muscle is an involuntary, non-striated (no bands) muscle associated with blood vessels and visceral organs.

• Smooth muscle contains overlapping protein myofilaments actin and myosin. The relative sliding of which produces shortening and generates force. This process involves cross bridge formation between actin and myosin which is driven by ATP. - similar to skeletal muscle, but slow contraction compared to skeletal muscle

• Coupling between the membrane action potential and contraction is mediated by the calcium ions. Ca++ regulates myosin to enable cross bridge formation and contraction.

• Smooth muscle is regulated by the autonomic nervous system. Some smooth muscle is regulated by stretch (mechanical channels, like blood vessels expanding allow Ca+ flow) and/or by paracrine factors

• In pacemaker cells, action potentials are initiated by an influx of extracellular Ca++.

• Some smooth muscle exhibits fused tetanus (tension - phasic) and tonic contraction. e.g. Tonic - sphincter.

 

Cardiac Muscle

Involuntary muscle found in heart and vena cava (large veins head to heart) and pulmonary veins (lung to heart)