Chapter 12: Muscles

Muscular dystrophy

DMD: early childhood onset, severe, survival to late 20s BMD: adolescent or adult onset, less severe, survival to mid-late adulthood - lack of dystrophin - degradation of muscle cells

Ratio of MLCK activity to MLCP activity

Determines contracting vs. relaxing MLCP is always somewhat active MLCK>MLCP = contraction MLCK<MLCP = relaxation

Myosin is formed

Each myosin is composed of protein chains that intertwine to form a long tail and a pair of tadpole like heads. rodlike tail is stiff but the protruding heads have an elastic hung region where the heads join the rods. This hinge region allows the heads to swivel around their point of attachment

What are some chemical influences on smooth muscle?

Effects may be excitatory or inhibitory - examples of modulation: GPCR -- activate GPCR PLC signal transduction pathway - increase DAG = increase [IP3] = increase SR Ca2+ release - increase DAG = inhibit MLCP activity OVERALL effect: contract or relax? - contract? -- activate GPCR-adenylyl cyclase signal transduction pathway - increase [cAMP] = inhibit IP3 = decrease SR Ca2+ release - K leak channels allow K to flow out = hyperpolarize cell and decrease voltage gated Ca2+ channel activity - increased MLCP activity OVERALL effect: contract or relax? relax?

What two filaments slide past each other during contraction?

actin and myosin

What do myosin heads bind to?

actin molecules (aka the rope)

Contraction and relaxation is slow in smooth muscle, why?.

action is coordinated with other functions myosin ATPase activity is slow - slow crossbridge cycling

Rattlesnake toxin (crotoxin)

acts on motor neurons (also has CNS effects and cytotoxicity) decreases NT release at Neuromuscular junction - resp. failure Other rattlesnake toxins are hemotoxins

Black widow spider venom (a- latroxin)

acts on motor neurons and endocrine cells makes a pore in the membrane that allows Ca2+ into the axon terminal - increases NT release at neuromuscular junction - increase muscle contractions = spasms and rigidity - followed by paralysis due to depletion of NT: may cause resp. failure

What are the transverse or t-tubules?

adjacent to and closely associated with the terminal cisternae branching network are extensions of the cell membrane that associate with the terminal cisternae of the SR one T-tubule and its two flanking terminal cisternae are called a triad. the lumen of the t-tubules are continuous w/ECF

What do t-tubules allow to happen?

allow action potentials to move rapidly from the cell surface into the interior of the fiber so that they reach the terminal cisternae nearly simultaneously. w/out t-tubules, the AP would reach the center of the fiber only by conduction of the AP through the cytosol, a slower and less direct process that would delay the response time of the muscle fiber.

What is motor unit recruitment?

allows variation in tension development - activate more somatic motor neurons - activate different types of motor units (slow vs fast)

What is an isotonic contraction?

any contraction that creates force and moves a load eccentric: lengthening contraction (contributes most to cellular damage after exercise and leads to delayed muscle soreness) Concentric:

What is central fatigue?

arise in the CNS neuronal control

Denervation or disuse

atrophy reduced diameter of myofibers reduced metabolic activity

Curare

binds to ACh receptors but doesn't open ion channels decreases muscle action

C. botulinum (toxins A-G)

blocks NT release (inhibits SNARE) to excitatory neurons - reduces muscle contractions (botox)

C. tetani

blocks NT release (inhibits SNARE) to inhibitory neurons - severe muscle contractions

How can smooth muscle be categorized?

by location contraction pattern electrical signaling

How are the parallel thick and thin filaments of the myofibril connected?

by myosin crossbridges that span the space between the filaments each G-actin molecule has a single myosin-binding site, and each myosin head has one actin binding site and one binding site for ATP.

How is skeletal muscle attached to bones?

by tendons made of collagen

Relaxation

End of contraction sequence: stop somatic motor neuron stimulation - voltage gated DHP channels are inactivated - Ryanodine channels close - Ca2+ no longer released into cytoplasm SR pumps Ca2+ back into its lumen using Ca2+-ATPase. Calcium releases from troponin Tropomyosin blocks actin's myosin-binding site As the crossbridges release, the muscle fiber relaxes with the help of elastic fibers in the sarcomere and in the CT of the muscle.

What are type 2b fibers?

Fast twitch glycolytic fibers fastest contraction fatigue quickly large increase in size = large increase in tension (maximal tension) large diameter least used jumping, quick fine movements

Anaerobic cellular respiration

Faster but lower ATP yield per glucose (2 ATP) short duration glucose and glycogen stores

Which parts of a sarcomere shorten during contraction?

H zone I band Z disks

Paracrine Agents

Histamine released in immune response (basophils and mast cells) - airway smooth muscle contraction: bronchoconstriction Nitric oxide (NO) released by endothelial cells - blood vessel smooth muscle relaxation: vasodilator

Hypoexcitability and reduced stimulation: muscle weakness

Hypercalcemia: high ECF [Ca2+] affects neuron excitability - decreased Na permeability - effect on neuron resting membrane potential: constant repolarization; weakness, shrinking (atrophy)

Membrane potentials and smooth muscle contraction

Hyperpolarized membrane potential: less likely to contract Slow wave potentials: regular oscillations, subthreshold depolarization, add'l stimulus necessary Pacemaker potentials: regular oscillations, depolarization to threshold, self-stimulating Pharmacomechanical coupling: no change in membrane potential, signal transduction pathways

Ca2+ in SR

Inositol triphosphate (IP3) receptor channel - pharmacomechanical coupling - activate GPCR and PLC signal transduction pathway - - increased [IP3] binds to SR IP3 receptor - - SR Ca2+ release Ryanodine receptors: - electromechanical coupling - RyR in SR - Ca2+ induced Ca2+ release - open when Ca2+ from ECF bind - SR Ca2+ release

ATP use in myofiber action (what is it used for?)

It is used during contraction for crossbridge movement and release(energizing myosin head and release of myosin after power stroke), during relaxation to pump Ca2+ back into the SR(Ca-ATPase), and after E-C coupling to restore Na and K to the Extracellular and intracellular compartments after myofiber AP. (Na/K ATPase)

Which two types of muscle have multiple levels of control? What are those levels?

cardiac and smooth primary extrinsic control arises through autonomic innervation, but some types of each can contract spontaneously, w/out signals from the CNS. the activity of both types of muscle is subject to modulation by the endocrine system.

Sarcolemma

cell membrane of a muscle fiber

H zone

central region of the A band, lighter than the outer edges of the A band because the H zone is occupied by thick filaments only.

What are skeletal muscles composed of?

collection of muscle fibers

Why are skeletal muscles unique?

contract only in response to a signal from a somatic motor neuron. cannot initiate their own contraction, and their contraction is not influenced directly by hormones.

Smooth muscles by contraction pattern

Phasic: alternate between relaxation and contraction tonic: always somewhat contracted - may increase or decrease level of contraction (esophageal and urinary bladder sphincters)

Isometric contraction

contraction creates force but doesn't move a load Force<load sarcomere length maintained pulls on elastic elements of the muscle (series elastic elements) - CT in sarcomeres, myofibers, and muscle - sarcomere shortening due to crossbridge cycling = elastic component stretch

Organs generally have multiple layers of smooth muscle, why?

contraction of organ can be in multiple directions

Smooth muscle Contraction

crossbridge cycling occurs process of crossbridge cycling is the same as in skeletal muscles

Sarcoplasm

cytoplasm of a muscle fiber

A band

darkest of the sarcomere's bands encompasses the entire length of a thick filament. at the outer edges of the A band, the thick and thin filaments overlap center of the A band is occupied by only thick filaments A = anisotropic (scatters light unevenly)

Myasthenia gravis

decrease sensitivity to ACh - Reduced EPP

What are general factors that may cause fatique?

dehydration low blood sugar and glycogen stores

Latch state

dephosphorylated myosin heads don't always release from actin maintains a level of tension without crossbridge cycling conserves energy

What happens at the end of the power stroke?

each myosin head releases actin, then swivels back and binds to a new actin molecule, ready to start another contractile cycle. during contraction, the heads do NOT all release at the same time or the fibers would slide back to their starting position

Contractions may be initiated by a variety of stimuli, including:

electromechanical coupling: changes in membrane potential - electrical signals and changes in membrane potential pharmacomechanical coupling: minimal changes in membrane potentials - chemical signals - mechanical signals

What are type 2a fibers?

fast twitch oxidative-glycolytic fibers - faster contraction - intermediate fatigue rate - increase size = increase tension medium diameter standing, walking,

What are antagonistic muscle groups?

flexor-extensor pairs in which one pulls a bone in one direction and the extensor pushes it back. they exert opposite effects

Give an example of an antagonistic muscle group.

flexor: biceps brachii extensor: triceps brachii

Cardiac Muscle

found only in the heart moves blood through the circulatory system Striated, smaller, branched, uninucleate cells are joined by junctions: intercalated disks. involuntary

The cytosol between the myofibrils contain many what?

glycogen granules and mitochondria glycogen: storage form of glucose, is a reserve source of energy mitochondria contain the enzymes for ox phosph of glucose and other biomolecules, producing much of the ATP for muscle contraction

Diseases

Pollomyelitis Muscular Dystrophy: DMD and BMD McArdle's Disease Myasthenia gravis

Ch. 25 stuff Muscle Metabolism

Rest Glycogen production & storage Phosphocreatine production & storage Exercise Aerobic Glucose & stored glycogen Fatty acids ↑ use at lower intensity ↑ use in longer duration Anaerobic Glucose Lactate production

What are fascicles?

groups of adjacent muscle fibers bundled together into units collagen, elastic fibers, nerves, and blood vessels are found between fascicles entire muscle is enclosed in a connective tissue sheath that is continuous with the connective tissue around the muscle fibers and fascicles and with the tendons holding the muscle to underlying bones.

What is nebulin?

helps titin is an inelastic giant protein that lies alongside thin filaments and attaches to the Z disk. Helps align the actin filaments of the sarcomere.

Hyperexcitability and excessive stimulation: tetanus

hypocalcemia: low ECF [Ca2+] affects neuron excitability - increased Na permeability - effect on neuron resting membrane potential: constant depolarization, = muscle cramp - doesn't go away until somatic motor neuron is inhibited by CNS

Nerve gas (Sarin)

inactivates ACh-esterase - cont'd presence of ACh causes cont'd depolarization of postsynaptic neuron - voltage gated Na channels inactivated - desensitization of ACh receptors

Myosin light chain phosphatase modulation

increase or decrease MLCP action at a constant [Ca2+] - contraction desensitized to Ca2+ --- decreased force development at [Ca2+] that should result in contraction - contraction more sensitive to Ca2+ --- increased force development at [Ca2+] that should not have as much contraction modulators: NTs, hormones, paracrine molecules - activate GPCR and phospholipase C (PLC) signal transduction pathway - - increased DAG inhibits MLCP activity - - increase [IP3] increases SR Ca2+ release

Isotonic contractions: load vs. shortening velocity

increased load = decreased shortening velocity greater the load, smaller shortening velocity of contraction

Isotonic contractions: load vs latent period

increased load = increased latent period greater the load, longer latent period

Muscle disorders can be influenced by:

influence of ECF [Ca2+]: hyperexcitability/hypoexcitability overuse/increased use: hypertrophy denervation/disuse: atrophy Toxins Diseases

Resting muscle tone

involuntary contraction of a small number of motor units - constantly alternate to avoid fatigue maintains constant tension on tendons and stabilizes position of bones and joints

What are glycolytic fibers?

large diameter fiber = more myofilaments decreased myoglobin, blood supply, and mitochondria - white fibers

What are the two states of crossbridges?

low-force (relaxed muscles) and high-force (contracting muscles)

Sarcoplasmic reticulum?

modified ER that wraps around each myofibril like a piece of lace consists of longitudinal tubules with enlarged end regions called terminal cisternae. concentrates and sequesters Ca2+ with the help of a Ca2+ -ATPase in the SR membrane Calcium release from the SR creates calcium signals that play a key role in contraction in all types of muscle

Myosin

motor protein with the ability to create movement Various isoforms of myosin occur in different types of muscle and help determine the muscle's speed of contraction.

What is the basic unit of contraction in an intact skeletal muscle?

motor unit composed of a group of muscle fibers that function together and the somatic motor neuron that controls them. somatic motor neuron and all myofibers innervated One AP = one twitch in all innervated myofibers - 1:1: most precision - 1: 700 - 1: 2000: most tension all myofibers in a motor unit are the same fiber type - fast vs slow twitch

How is F-actin formed?

multiple G-actin molecules polymerize to form long chains or filaments (F-actin). in skeletal muscle, two F-actin polymers twist together like a double strand of beads, creating thin filaments of the myofibril

McArdle's Disease

muscle cells lack myophosphorylase - can't convert glycogen to glucose - 6 - Phosphate

Myofibril proteins are:

myofilaments: myosin (thick filaments) Microfilaments: actin (thin filaments) Regulatory proteins: tropomyosin and troponin giant accessory proteins: titin and nebulin

Smooth muscle relaxation

myosin light chain phosphatase (MLCP): always somewhat active) myosin light chains are dephosphorylated myosin ATPase activity is reduced crossbridges may be released Latch state:

Pollomyelitis

neural damage - lack of stimulation - flaccid paralysis

What is rigor mortis?

occurs after death after death, when metabolism stops, and ATP supplies are exhausted, muscles are unable to bind more ATP, so they remain in the tightly bound rigor state. The muscles freeze (immovable crossbridges) The tight binding of actin and myosin persists for about a day or so after death, until enzymes released within the decaying fiber start to break down the muscle proteins.

Z disks

one sarcomere is composed of two Z disks and the filaments found between them. Z disks are zig zag protein structures that serve as the attachment site for thin filaments (actin attachment site)

What is the sliding filament theory of contraction?

overlapping actin and myosin filaments of fixed length slide past one another in an energy-requiring process resulting in contraction. Explains how a muscle can contract and create force without creating movement. tension generated in a muscle fiber is directly proportional to the number of high force crossbridges between the thick and thin filaments

What is passive tension?

passive stretch of the muscle - no APs - CT in sarcomeres, myofibers, and muscle - - like the tension developed in a rubber band when you stretch it

What are other sources of ATP?

phosphocreatine Cellular respiration: aerobic and anaerobic

What is the backup energy source of muscles?

phosphocreatine: high energy phosphate bonds are created from creatine and ATP when muscles are at rest. When muscles become active, the high energy phosphate group of phosphocreatine is quickly transferred to ADP, creating more ATP to power the muscles. Creatine + ATP ↔ phosphocreatine + ADP - short term: 10-15 seconds maximal exercise - creatine kinase: enzyme catalyst for both rxns (transfers phosphate group from phosphocreatine to ADP) -- released into bloodstream after muscle damage -- 2 isozymes: used to identify type of muscle damage - - - skeletal muscle - - - cardiac muscle - heart attack - increased blood levels. why have the three systems: comparison Ch. 25 image

Smooth Muscle

primary muscle of internal organs and tubes, like stomach, urinary bladder, blood vessels. primary function: to influence the movement into, out of and within the body small fibers, lack striations involuntary

Contractions can be maintained without fatigue, this allows for what?

prolonged contractions

M line

represents proteins that form the attachment site for thick filaments, equivalent to the Z disk for the thin filaments each M line divides an A band in half.

Muscle Fatigue

reversible condition in which an exercising muscle is no longer able to generate or sustain the expected power output. (loss of ability to develop or maintain tension) influenced by the intensity and duration of the contractile activity, by whether the muscle fiber is using aerobic or anaerobic metabolism, composition of muscle, and fitness level of individual.

What is Active tension

sarcomeres and myofibers - crossbridge cycling - actin and myosin interactions

Conversion of isometric to isotonic concentric contraction

shortening contraction requires an isometric contraction before the isotonic contraction isotonic contraction latent period - E-C coupling plus time for isometric contraction

Cardiac Muscle structure

single cells, branched intercalated disks - gap junctions: electrical synapse - desmosomes striated, sarcomeres - troponin and Ca2+ regulation

Which type of muscle makes up the bulk of the muscle in the body?

skeletal constitute ~40% of the body weight

What are type 1 muscle fibers?

slow twitch fibers or slow-oxidative fibers - slower contraction - resist fatique - decreased size = decreased tension small diameter used for posture (most used)

Aerobic Cellular respiration

slower but high ATP yield per glucose (30-32 ATP) longer duration glucose, glycogen stores, fatty acids

How are thick filaments arranged?

so that the myosin heads are clustered at each end of the filament, and the central region of the filament is a bundle of myosin tails

Overuse/increased use

soreness, fatigue, tears Hypertrophy - increased diameter of myofibers - increased metabolic activity

The length of what remains constant during contraction?

the A band of a myofibril (A band represents myosin)

What is the sarcomere? What are the elements of the sarcomere?

the contractile unit of the myofibril Z disks I band A band H zone M line

What is contraction?

the creation of tension in a muscle, an active process requiring ATP

What is the origin of a muscle?

the end of the muscle that is attached closest to the trunk or to the more stationary bone

I band

the lightest color bands of the sarcomere and are a region occupied only by thin filaments I = isotropic a Z disk runs through the middle of every I band, so half of an I band belongs to a different sarcomere

What are myofibrils?

the main intracellular structures in striated muscles highly organized bundles of contractile and elastic proteins that carry out the work of contraction

What is the insertion of a muscle?

the more distal or more mobile attachment

What is the heavy chain of the myosin head?

the motor domain that binds ATP and uses the energy from ATP's high energy phosphate bond to create movement. The motor domain acts as an enzyme, so it is considered a myosin ATPase. contains a binding site for actin

What provides the force that pushes the actin filament during contraction?

the movement of myosin crossbridges

What does troponin control?

the positioning of an elongated protein polymer, tropomyosin. the off-on positioning of tropomyosin

What is relaxation?

the release of tension created by a contraction

How are skeletal muscle fibers formed?

they are the largest cells in the body, created by fusion of many individual embryonic muscle cells. Committed stem cells (satellite cells) lie just outside the muscle fiber membrane, and become active and differentiate into muscle when needed for muscle growth and repair.

The proper alignment of filaments within a sarcomere is ensured by two proteins: what are they?

titin and nebulin

How many protein chains does each myosin head have?

two protein chains: a heavy chain and a smaller light chain.

Smooth muscles by Location

vascular gastrointestinal urinary respiratory reproductive ocular

Ca2+ in ECF for sm. muscle

voltage gated channels: electromechanical coupling - graded potentials open voltage gated Ca2+ channels - Ca2+ enter cell results in rapid depolarization ligand gated channels: pharmacomechanical coupling - ligand binding to receptor opens Ca2+ channels Mechanically gated channels: stretch activated - stretch activated channels open when cell membrane is stretched or distorted - - opens Ca2+ channels and depolarizes the cell - - myogenic contraction: originates in smooth muscle cell itself

What is the power stroke?

when myosin crossbridges swivel and push the actin filaments toward the center of the sarcomere. repeats many times as the muscle fiber contracts. the myosin heads bind, push and release actin molecules over and over as the thin filaments move toward the center of the sarcomere.

When do crossbridges form?

when the myosin heads of thick filaments bind to actin in the thin filaments.

Smooth muscle is capable of contracting over wide range of lengths.. explain

wider range for optimal length and force generation storage organs range from empty to filled, (stomach)

What are the four major events of E-C coupling?

1. ACh is released from the somatic motor neuron 2. ACh initiates an AP in the muscle fiber 3. The muscle AP triggers calcium release from the SR 4. Calcium combines with troponin and initiates contraction

Myofiber length and active tension

Resting myofiber length - Optimal length(Lo): greatest development of tension -- optimal overlap between actin and myosin --- = 95% Lo - 105% Lo: maximal tension development --- = 70% Lo and ~150% Lo - 50% max tension developed Decreased length: too much overlap ~60% Lo and below: no tension Increased length: too little overlap ~175% and above = no tension IF fibers start a contraction at a very long sarcomere length, the thick and thin filaments barely overlap and form few crossbridges. Optimum sarcomere length forms many crossbridges. creates optimum force. IF fibers start at shorter than optimum, the thick filaments can move the thin filaments a short distance before actin filaments from opposite ends of the sarcomere start to overlap. prevents crossbridge formation. If the sarcomere is so short that the thick filaments run into the z disks, myosin is unable to find new binding sites for crossbridge formation, and tension decreases rapidly.

Smooth muscle by electrical signaling

Single unit (visceral) smooth muscle: cells are electrically connected by gap junctions, and contract as coordinated unit (most are this) Multi-unit smooth muscle: cells are NOT linked electrically and each muscle cell functions independently (individual chemical synapses w/ varicosities) (iris and ciliary muscle of the eye, and in the uterus just prior to delivery)

What are oxidative fibers?

Small fiber diameter = fewer myofilaments (actins and myosins) increased myoglobin, blood supply and mitochondria -- red fibers: myoglobin causes it ---- lots of oxygen available for aerobic cellular respiration

Timing of E-C coupling

Somatic motor neuron AP is followed by the skeletal muscle AP which is followed by contraction.

Molecular events of the contraction cycle in skeletal muscle

Start cycle in rigor state, where myosin heads are tightly bound to G-actin (not bound to ATP or ADP) 1. ATP binds and myosin detaches. ATP binds to myosin head. ATP binding decreases the actin-binding affinity of myosin, and myosin releases from actin 2. ATP hydrolysis provides energy for the myosin head to rotate and reattach to actin. The ATP-binding site on the myosin head closes around ATP and hydrolyzes it to ADP and Pi. ADP and Pi remain bound to myosin as energy released by ATP hydrolysis rotates the myosin head until it forms a 90 degree angle with the long axis of the filaments. In this cocked position, myosin binds to a new actin that is 1-3 molecules away from where it started. The newly formed actin-myosin crossbridge is weak and low force because tropomyosin is partially blocking actin's binding site. The myosin head is cocked and prepared to contract, just waiting for a calcium signal. 3. The power stroke. Begins after Ca2+ binds to troponin to uncover the rest of the myosin binding site. The crossbridges transform into strong, high force bonds as myosin releases Pi - which allows the head to swivel. The head swings toward the M line, sliding the attached actin filament along with them. Myosin head tilts from 90 to 45 angle. 4. Myosin releases ADP. At the end of the power stroke, myosin releases ADP, causing the myosin head to again tightly bind to actin in the rigor state. cycle is ready to begin again as a new ATP binds to myosin.

Electrochemical coupling of smooth muscle

1. depolarization opens voltage gated Ca2+ channels 2. Extracellular Ca2+ and Ca2+ from SR enter cytosol 3. Ca2+ binds to calmodulin 4. Activation of calmodulin activates myosin light chain kinase (MLCK) 5. Myosin light chains are phosphorylated 6. Myosin ATPase activity is enhanced 7. crossbridges form & crossbridge cycling occurs

What are the two functions of titin?

1. it stabilizes the position of the contractile filaments 2. its elasticity returns stretched muscles to their resting length

How many myosin molecules join to create a thick filament?

250 myosin molecules

The amount of ATP stored in a muscle fiber at any one time is sufficient for only about how many twitches?

8

Which parts of a sarcomere do not shorten?

A band remains constant

What is a myofiber twitch?

A single contraction-relaxation cycle in a skeletal muscle fiber - one neuron AP - one myofiber AP - Myofiber contraction -- latent period: short delay between muscle AP and the beginning of muscle tension development. (represents time required for calcium release and binding to troponin) -- contraction phase -- relaxation phase

What is summation?

AP duration (1-3 ms) vs twitch duration (100 ms) - single twitch - summation - - incomplete or unfused tetanus - partial relaxation - - complete or fused tetanus - no relaxation

Where does energy for the power stroke come from?

ATP. Myosin converts chemical energy from ATP into mechanical energy of crossbridge motion. Myosin is an ATPase that hydrolyzes ATP to ADP and Pi. The energy released by ATP hydrolysis is trapped by myosin and stored as PE in the angle between the myosin head and the long axis of the myosin filament. myosin heads in this position are said to be "cocked", or ready to rotate. The PE of the cocked heads becomes KE in the power stroke that moves actin.

What is the structure of smooth muscle?

Actin and myosin: - more actin surrounding myosin than in skeletal muscle - longer myosin filaments, fully covered by myosin heads --- recall: optimal length in force development - no troponin, so no tropomyosin regulation - no sarcomeres -- myosin molecule surrounded by actin -- actin anchored to dense bodies throughout cell ---- dense bodies anchored to cell membrane SR: less developed, still associated with cell membrane Caveolae: - cell membrane invaginations - close association with SR - not as extensive as the T-tubule

Less energy is required for maintenance of tension in smooth muscle. What does this allow for?

Allows prolonged contractions

What is asynchronous motor unit recruitment?

Alternate which motor units are activated reduce muscle fatigue (only prevents fatigue in submaximal contractions; in high tension, sustained contractions the motor units may reach a state of unfused tetanus)

How does a calcium signal turn muscle contraction on and off?

Answer is found in troponin (TN), a calcium binding complex of three proteins. in resting skeletal muscle, tropomyosin wraps around actin filaments and partially covers actin's myosin-binding sites. This is tropomyosin's blocking or off position. Weak, low force actin-myosin binding can still happen, but myosin is blocked from completing its power stroke. Before contraction can occur, tropomyosin must be shifted to an "on" position that uncovers the remainder of actin's myosin-binding site.

Autonomic NTs and hormones

Antagonist control: symp vs parasymp - diff NTs and diff receptors = diff responses Same NTs and diff receptors = diff responses - adrenergic receptor isoforms - a-adrenergic receptors and epinephrine = smooth muscle contraction - B-adrenergic receptors and epinephrine = smooth muscle relaxation tonic control: only one system controls - graded response: amount of NT determines amount of contraction

What is peripheral fatigue?

Arise anywhere between the neuromuscular junction and the contractile elements of the muscle Myofiber AP: with increased myofiber activity, overall loss of K+ to ECF which reduces the ability of the myofiber to repolarize and voltage gated Na channels to remain open or inactivated --> no additional myofiber APs. - 1 AP produces 1 twitch Excitation-contraction coupling: lack of Ca2+ or Ca2+ binding to Pi reduces ability to bind to troponin crossbridge cycling: high levels of cytoplasmic ADP and Pi may inhibit release of ADP from myosin.

Skeletal Muscle

Attached to bones of the skeleton enables muscles to control body movement striated (alternating light and dark bands under light microscope) fibers are large, multinucleate cells, striated voluntary

What system controls smooth muscle?

Autonomic parasympathetic control: sphincter of iris sympathetic: radial muscle of iris

Cardiac Muscle Neural control

Autorhythmic - Autonomic system influence - - parasympathetic w/ ACh, sympathetic with NE and hormone epinephrine involuntary

Toxins

C. tetani C. botulinum (A-G) Black widow spider venom (a-latroxin) rattle snake toxin (crotoxin) Curare Nerve gas

What must happen for muscle relaxation to occur?

Ca2+ conc. in the cytosol must decrease. By the law of mass action, when cytosolic calcium decrease, Ca2+ unbinds from troponin. in the absence of Ca2+, troponin allows tropomyosin to return to the "off" position, covering most of actin's myosin binding sites. During the brief portion of the relaxation phase when actin and myosin are not bound to each other, the filaments of the sarcomere slide back to their original positions with the aid of titin and elastic connective tissues within muscle.

Ca2+ ATPase pump returns Ca2+ to ECF or to SR, how?

Ca2+ released from calmodulin MLCK inactivated MLCP active Myosin light chain dephophorylated Myosin ATPase activity is reduced Crossbridge cycling reduced

What is an extensor?

a muscle that contracts to move the skeleton the bones move away from each other when the muscle contracts, movement = extension

What is a flexor?

a muscle that contracts to move the skeleton the centers of the connected bones are brought closer together when the muscle contracts, movement = flexion

What is actin?

a protein that makes up the thin filaments of the muscle fiber. one actin molecule is a globular protein (G-actin)

How many myofibrils are in a muscle fiber?

a thousand or more that occupy most of the intracellular volume, leaving little space for cytosol and organelles. each myofibril is compose of several types of proteins organized into repeating contractile structures (sarcomeres)

What is the load?

a weight or force that opposes contraction of a muscle

What is muscle tension?

The force created by contracting muscle

At the molecular level, transduction of the electrical signal into a calcium signal requires two key membrane proteins. What are they?

The t-tubule membrane contains a voltage-sensing L-type calcium channel protein called dihydropyridine (DHP) receptor. DHP receptors, FOUND ONLY in skeletal muscle, are mechanically linked to Ca2+ channels in the adjacent SR. They are voltage gated and found in sarcolemma These SR Ca2+ release channels are AKA ryanodine receptors (RyR) (in the SR and mechanically gated) - Ca2+ is released to cytosol - Tropomyosin shifts - contraction initiates. AP reaches DHP receptor, changes conformation which opens RyR Ca2+ release channels in SR. Stored Ca then flows down electrochem. gradient into cytosol and initiates contraction.

Moving tropomyosin to the on position explained:

When contraction begins in response to a calcium signal, 1. one protein of the complex (troponin C) binds reversibly to Ca2+ 2. The calcium-troponin C complex pulls tropomyosin completely away from actin's myosin-binding sites 3. This "on" position enables the myosin heads to form strong, high-force crossbridges and carry out their power strokes. 4. moving the actin filament 5. Contractile cycles repeat as long as the binding sites are uncovered.

What initiates the power stroke?

a calcium signal

What is titin?

a huge elastic molecule and the largest known protein, composed of more than 25,000 amino acids. A single titin molecule stretches from one Z disk to the neighboring M line.

E-C coupling events in detail

1. ACh released into the synapse at a neuromuscular junction binds to ACh receptor-channels on the motor end plate of the muscle fiber. 2. When the ACh-gated channels open, they allow both Na and K to cross the membrane. However, Na influx exceeds K efflux because the electrochemical driving force is greater for Na. The addition of net positive charge to the muscle fiber depolarizes the membrane, creating an end-plate potential (EPP) - Normally, EPPs always reach threshold and initiate a muscle action potential --- Na movement > K movement --- EPSP 3, 4. The AP travels across the surface of the muscle fiber and into the t-tubules by the sequential opening of voltage gated Na channels. (Na+ depolarization, K+ repolarization) The AP that moves down the t-tubules causes Ca2+ release from the SR. (AP spreads BIdirectionally along the sarcolemma and down the t-tubule) 5. Free cytosolic Ca2+ levels in a resting muscle are normally quite low, but after an AP, they increase ~100 fold. (When cytosolic Ca2+ levels are high, Ca2+ binds to troponin, tropomyosin moves to the "on" position. 6. Contraction occurs.

Summary Map of Muscle contraction

1. Events at the neuromuscular junction convert an ACh signal from a somatic motor neuron into an electrical signal in the muscle fiber 2. Excitation-contraction (E-C) coupling is the process in which muscle action potentials initiate calcium signals that in turn activate a contraction-relaxation cycle. 3. At the molecular level, a contraction-relaxation cycle can be explained by the sliding filament theory of contraction. In intact muscles, one contraction-relaxation cycle is called a muscle twitch.

How can muscle fiber types be classified?

By maximal velocities of shortening: fast twitch, slow twitch By Pathways of ATP production and rates of fatigue: oxidative fibers, glycolytic fibers. By combinations of Velocity and ATP production: type 1, 2a, 2b

Calcium and contraction: 2 sources of Ca2+ in smooth muscle

ECF and SR

What are slow twitch fibers?

Myosin w/lower ATPase activity Lower Ca2+ ATPase activity

What are fast twitch fibers?

Myosin with high ATPase activity - crossbridge cycling is 2-3 times faster than slow twitch. High Ca2+ ATPase activity - returns Ca2+ to SR faster than slow twitch