Muscle Contractions Physiology

Skeletal vs smooth vs Cardiac muscle

Skeletal= Voluntary, multinucleate, striated (40%)

Smooth= Involuntary, unstraited, single nuclei

Cardiac= involuntary, striated, single nuclei

Cardiac + smooth makes up 10% of body mass

Breakdown of skeletal muscle

Myosin and Actin, Sarcomeres, myofibrils, myocyte, Muscle fibers, Muscle

Muscle belly is the fleshy, central, bulging portion of the muscle

Sarcolemma

Outer membrane of muscle cell. Consists of cell membrane plus outer polysaccharide layer attached to tendons

What is the contractile unit of muscle

Sacromere

Structure of sacromere

Made of actin and myosin, plus titin

Actin=thin contractile protein filament attached to Z band

Myosin= thick contractile protein filament arranged in center of sacromere

Z-line= thin, non-contractile protein band, serves as anchor

H zone= only myosin

I band = only actin, light band

A band = dArk section where actin and myosin overlap

Arrangement of actin, troponin, tropomyosin, and myosin, including binding sites

Tropomyosin sits on top of myosin binding cite on actin. Troponin is attached to tropomyosin. Myosin has intertwined helical tails with globular head, the heads are what bind to actin as well as binding actin

Structure and function of sarcoplasmic reticulum

Smooth-surfaced tubules that surround each myofibril, serve as an intracellular organelle for calcium storage

Structure and function of t-tubules

Formed by invaginations of the sarcolemma and are filled with extracellular fluid, forms junctions with SR, allowing for the spread of AP into the interior of the muscle fiber

Outline the steps involved in transmission of an AP from a motor neuron to a skeletal muscle cell

1. AP in neuron opens Vgated calcium channels in the axon terminal

2. Influx of Ca binds synaptotagmin on vessicles

3. Exocytosis of Acetylcholine

4. ACh binds nicotinic AChR, allowing influx of Sodium and calcium and efflux of potassium

5. AP propagates down sarcolemma, through T-tubules

6. More Vgated Na channels open

7. AP propagates along the membrane

Outline the path of propagation of AP along a skeletal muscle cell membrane starting from point of initiation and proceeding to the region where excitation-contraction coupling occurs

AP propagates down t tubules, this opens Vgated Caclium channels DHPRs that allows calcium into intracellular fluid. DHPR opening is coupled with RyRs (calcium release channels expressed on SR membrane) which allows SR calcium into intracellular fluid.

Calcium is required for myocyte contraction,

SERCA vs DHPR vs RyRs

Sarco/endoplasmic reticulum calcium ATPase pumps calcium into SR against concentration gradient

Dihydropyridine receptors are expressed on t tubules and are voltage gated calcium channels that allow calcium to flow into cell

Ryanodine receptors are calcium induced/DHPR couple calcium ion channels on SR that allow calcium out of SRs

Is calcium concentration low or high in SR, Extra and intracellular fluid

High in EC fluid and SR, low in IC fluid

Describe the structural changes associated with sarcomere shortening and how these changes produce shortening of the entire muscle

With sufficient calcium and ATP, Actin filaments are pulled in parallel along myosin filaments, increasing overlap from power strokes, pulls Z bands closer together

Outline ATP-mediated steps associated with skeletal muscle contraction and relaxation

When Myosin heads are bound to ATP, low affinity for actin

The ATPase associated with myosin head PARTIALLY hyrdrolizes ATP into ADP and Pi that are still bound to myosin head, this increase affinity for actin

Binding to actin (cross-bridging) stimulates complete hydrolysis of ATP and myosin releases the phosphate.

Release of phosphate causes conformational change forcing the flexion of myosin and pulling actin filament and shortening the sarcomere

After flexion, myosin heads will release ADP and bind a new ATP

Binding of ATP releases myosin from actin

What are the primary cellular mechanisms for producing ATP in skeletal muscle

Oxidative phosphorylation= aerobic process that produces 30 atp per glucose molecule

Glycolosys= anaerobic process that results in 2 ATP and can produce lactic acid

Creatine phosphate can quickly donate Pi to ADP to make ATP (mediated by creatine kinase), rapidly depleted. NOT the same as creatinine

What are the different muscle types and how do they differ based on ATPase activity, metabolic pathway, blood flow, mitochondrial content, myoglobin content, fatigue resistance, functional role, and recruitment order

Slow-twitch red, Fast-twitch white, Fast twitch red

Slow: slow ATPase activity, oxidative metabolism, large amount of blood flow, many mitochondria, high resistance to fatigue, used for posture, large amount of myoglobin, recruited first

Fast twitch white: Fast ATPase activity, glycolysis, less blood flow, less mitochondria, less myoglobin, fatigue rapidly, used for high speed and quick movement like jumping, recruited last

Fast twitch red: Intermediate ATPase activity, use both aerobic and anaerobic metabolism, relatively large amount of blood flow, mitochondria, and myoglobin, intermediate resistance to fatigue, used for walking, recruited before fast twitch white but after slow twitch red

Motor unit vs motor neuron pool

Motor unit= an alpha motor neuron and all the skeletal muscle fibers it innervates. All fibers in the motor unit are all the same type

Motor unit pool= consists of the neuronal cell bodies in the CNS associated with a single muscle belly

How does Summation (temporal summation) vs Recruitment (spatial summation) differ

Summation = leads to higher frequency of motor unit activation so myocytes are stimulated again before they have had time to relax leading to greater contractile force on the motor unit

Recruitment = multiple motor units contract at one time, occurs as demand of the muscle increases, increasing contractile force on the muscle belly

Tetany

When muscles contract without relaxation and is the result of maximal summation and recruitment

What is fatigue, what are the primary causes

Occurs when muscle has reduced ability to generate contractile force.

Nervous fatigue= motor neuron is unable to sustain a high frequency signal

Metabolic fatigue= There is a shortage of ATP and/or an excess accumulation of metabolites within a muscle fiber. Certain metabolites can interfere with either calcium release from SR or sarcomere sensitivity to calcium

Define the length tension relationship associated with skeletal muscle contraction, what is the importance of actin-myosin overlap and normal anatomy

Describes the muscle length in which a maximal contractile force can be produced, depends on overlap of myosin and actin. Too little overlap = not enough cross bridge formation, too much overlap means actin associates with myosin tails rather than myosin heads

What is the relationship between load and contraction velocity

Reciprocal relationship between load and velocity of contraction. As load increases, velocity decreases

Skeletal muscle hypertrophy and atrophy, what are causes

Hypertrophy= enlargement of muscle due to increased in cell size NOT cell number. Can result from working out

Atrophy= decreased cell size. Can result from denervation, loss of tendon attachment, immobilization, wieghtlessness

Isometric vs Isotonic contraction

Isometric= contraction rather does not involve any change in muscle length (only opposes load)

Isotonic = contraction that only involves a change in muscle length

Smooth vs skeletal muscle size, shape, nucleus, and sacromere orientation

Smooth muscle cells are smaller and shorter than skeletal, smooth muscle cells are uninucleate and their arrangement of sarcomeres are irregular, attaching to dense bodies rather than Z-lines

What are dense bodies

Located in cytoplasm and cell membrane of smooth muscle cells. Scattered arrangement. Actin filament bind to these instead of Z lines

Single unit (visceral) vs multi unit smooth muscle cells

Single unit = functional syncytium (a group of cells which the cytoplasm of one cell is continuous with that of adjoining cells, resulting in a multinucleate unit). This type of smooth muscle is in most internal organs, gap junctions exist between adjacent cells, cell to cell propagations of AP and coordinated muscle contraction

Multi unit = electrically isolated from each other. This type is used for very precise control of muscle contractions and is found in delicate tissue like the iris or ciliary body of the eye

Physic vs tonic smooth muscle and their locations

Physic/rhythmic = spends large portion of its time relaxed, only contracts periodically. GI tract, bladder

Tonic/continous = spends most of time contracted, only temporarily relaxes. Lower esophageal sphincter, blood vessels

Describe basic components of neural regulation of smooth muscle including nervous system involved, primary neurotransmitters and pattern of innervation

Regulated by ANS neurons. Primary neurotransmitters are ACh and norepinephrine. A single smooth muscle cell can receive input from more than one neuron

Single-unit smooth muscle is diffusely innervated (individual cells may not be innervated)

Multi unit must be individually innervated

How do membrane depolarization and receptor activation promote smooth muscle contractoin

Smooth muscle cells express Vgated Ca channels within caveolae (shallow membrane depressions).

Smooth muscles can also express different metabotropic receptors. Gq linke GPCR activates phospholipase C which promotes synthesis of DAG and IP3 which then go to allow influx of calcium into cytoplasm from ER

What are the names, locations, and functions of the primary transport proteins responsible for maintaining low cytoplasmic Ca in smooth muscle cells

Getting rid of Ca is slower in smooth compared to skeletal muscle

Smooth muscle express SERCA on ER, pumping Ca from cytoplasm into ER.

They also have Membrane Ca transporters 3Na-Ca exchanger and Ca ATPase. They use secondary and primary active transport respectively

Outline the calcium mediated steps with smooth muscle contraction and relaxation

Contraction relies on activation of myosin head ATPase.

Calmodulin binds calcium and becomes active. The Ca Calmodulin complex bind and activate myosin light chain kinase (MLCK). MLCK phosphorylates myosin and thus activates myosin ATPase

Explain why Gq promotes smooth muscle contraction while Gs inhibits

Gq GPCR is an alpha 1 adrenergic receptor. Its signalling cascade leads to the release of Ca

Gs GPCR is a beta 2 adrenergic receptor. It’s activation leads to cAMP which inhibits MLCK

How does myosin light chain phosphotase influence smooth muscle contractions during different phases of contraction cycle

Dephosphorylates myosin

If this happens when myosin is unattached to actin then cell is unable to contract

IF this happens when myosin is attached to actin then contraction is prolonged - is helpful for tonic smooth muscle