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Organismal Lec X 01/25/00 Lecture 6: Muscle Physiology

ASST.: READ CH. 10

I. Purpose A. In order to have N.S. produce behavior it must be able to act on effectors B. Neurons only produce electrical changes C. Need another TRANSDUCTION from electrical to mechanical or chemical energy D. Two main systems 1. Muscle - mechanical 2. Endocrine - Chemical (can lead to mechanical) II. Move down STRUCTURAL PYRAMID of Muscle A. Muscle attached via tendon to bone

Bone Muscle

B. Muscle is made up of MUSCLE FIBERS (CELLS) C. Muscle fiber (MULTINUCLEATED CELL) contains D. made up of THICK AND THIN FILAMENTS 1 Organismal Lec X 01/25/00 1. Thick - 2. Thin - 3. Together complex is called ACTOMYOSIN E. Filaments made of actin and myosin molecules III. Organization of (in myofibrils) A. Sarcomere

A Band

Z Line H Zone

I Band

B. Look at sarcomere more closely (Shows filament types associated with bands Sarcomere

A Band Myosin

Z Line H Zone Actin I Band

2 Organismal Lec X 01/25/00 IV. A. Originally thought proteins contract (shorten) B. Huxley and Niedergerke use light microscope to look at sarcomere length 1. Showed that A - Bands maintain constant width during contraction 2. I - Bands and H - zone becomes narrower 3. Stretch → I - Bands and H - Zone get wider a) A - Band again stays constant C. Hanson and H.F. Huxley measure protein length during contraction of live muscle D. Protein length does not change E. Two Huxleys independently put forward SLIDING FILAMENT THEORY 1. Contraction of sarcomeres is due to actin sliding past myosin 2. Protein size unaffected 3. Predict changes in H - Zone and I - Band F. Length - Tension curve supports sliding filament theory 1. Stretch and hold the length of sarcomeres 2. Stimulate and measure tension

1.2 1 0.8 0.6

0.4 Tension 0.2

01.25 1.65 2.00 2.25 3.65 Sarcomere Length

3 Organismal Lec X 01/25/00 3. Start at right a) Long length → little overlap → little tension b) Less stretch → more overlap → more tension c) 20% rest lengths → max overlap → max tension d) Smaller sarcomere → overlap of actin filaments → less tension e) Eventually myosin hits Z - line and crumples → 0 tension f) Tension is a function of cross-bridges formed between actin and myosin and is thus a function of overlap V. Structure responsible for Sliding filaments A. Structure of filaments 1. Structure of filaments and cross bridge formation a) To understand how tension is related to overlap of filaments b) first look at structure of filaments 2. F - actin (fiber-like) a) Two strings of beads wound around each other

3. G - actin a) Globular b) beads in f - actin c) each bead is a G - actin molecule B. MYOSIN FILAMENT 1. Bundle of myosin molecules 2. Myosin molecule

4 Organismal Lec X 01/25/00 Heads

Tail

3. Head is locus of ALL ENZYMATIC activity and ACTIN BINDING SITE 4. Myosin molecules aggregate with heads pointing out a) results in myosin filament

b) Actin + Myosin → Actomyosin C. How does actomyosin complex form and Move 1. One idea a) If head can rotate it can slide actin backward → shortening of sarcomere

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2. Myosin cycle a) attach to actin b) power stroke moves head ~ 10 nm c) detachment d) start of new cycle 3. Energetics of Myosin Cycle

Thin filament Cross Bridge

Energized Binds to Actin

C.B,

Thick fil. Z Line A + M*- ADP - Pi A-M* - ADP-P

Hydrolysis of Cross Bridge

ATP Energizes CB ADP + Pi Moves

ATP

ATP binds to Myosin Causing CB to Detach A + M-ATP A-M Complex

a) myosin hydrolyzes ATP in myosin complex b) energizes Myosin c) Myosin Binds to Actin d) Forms Crossbridge - ADP+Pi removed e) causes head to rock f) Myosin head rocks - slides actin

6 Organismal Lec X 01/25/00 g) ATP binds to myosin - causes head to detach D. At end of slide head is detached 1. Head can then grab on again 2. Thus, actin is passed from head to head 3. Detachment REQUIRES that ATP binds to the ATPase site on the myosin a) In absence of ATP (1) ALL heads BIND (2) RIGOR MORTIS b) ATP is then cleaved to energize myosin so it is ready for next cycle VI. What INIITIATES SLIDE A. Low levels of Ca required for B. Isolate actin and myosin 1. put in salt solution 2. actin and myosin will combine spontaneously to → actomyosin 3. with Ca, Mg and ATP added actomyosin will contract C. Strip away two proteins from actin filament 1. 2. D. Ca no longer required E. Troponin and Tropomyosin → tonic inhibition to actin and myosin binding (Ebashi) F. Ca turns off this inhibition G. Troponin -Tropomyosin Model 1. Tropomyosin covers myosin binding site on actin 2. Troponin binds Ca and undergoes conformational change a) Actually troponin is a complex of 3 subunits (1) C (2) T (3) I b) Ca binds on C subunit

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Ca Binding Sites C Tropomyosin

Filament T I

Myosin Head

Myosin

Binding

Site

Actin

3. Change in troponin draws tropomyosin away from the myosin binding site 4. So myosin can reach its binding site and binds spontaneously 5. Removal of Ca returns troponin and tropomyosin to original state 6. Inhibition of myosin resumes 7. Need > 10-7M Ca conc. to → contraction H. How is Ca level controlled? 1. Depolarize near Z line get contraction on either side 2. Level of depolarization determines DEPTH of CONTRACTION 3. At Z - line is tubule which penetrates muscle fiber to deep fibrils 4. Called T - tubules 5. Adjacent to T - tubules covering all fibrils from Z - line to Z - line is 6. Next to T - tubules S.R. forms terminal cisternea (pockets)

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T Tubule Terminal Cisternea

Sarc. Retic.

a) terminal cisternea + T - tubule = 1 Triad 7. Ca is actively sequestered in cisternea a) as a result Free Ca conc. < 10-7M 8. Motor neuron → A.P. in muscle fiber a) travels along membrane AND DOWN T - TUBULES b) Depol. of T - tubules → release of Ca from cisternea c) Can visualize Ca++ release with Ca++ sensitive dyes d) Plunger Model for Release of Ca++ from SR (1) Depolarization of T Tubule membrane Æ comformational change in voltage sensitive Dihydropyridine receptor (2) Dihydropyridine then pulls on ryanodine receptor (feet) that act as a plunger in SR keeping Ca++ from flowing out. (3) With ryanodine feet pulled out Ca++ can flow out and bind with troponin

9 Organismal Lec X 01/25/00 Dihydropyridine Receptor

++++ ++++ ------++++ ++++

------++++ ++++ ------

Ryanodine Receptor ATP Ca Ca Ca Ca

e) Free Ca conc. →10-6 M or higher Æ binding to troponin etc. leading to contraction f) ATP is then used to pump Ca++ back into SR against concentration gradient 9. This is EXCITATION - CONTRACTION COUPLING

Ca

Ca

VII. Muscular Movement – MECHANICS A. Muscle is not all contractile protein 1. Stretchy connective tissue in parallel with cont. proteins

10 Organismal Lec X 01/25/00 2. This constitutes the PARALLEL ELASTIC COMPONENT 3. There is also a SERIES ELASTIC COMPONENT a) Stretchy connective tissue in series with filaments (1) tendons (2) elasticity of heads

Contractile

Proteins

SEC

Weight

B. In order to move weight, muscle must first overcome SEC 1. Pull on weight via spring 2. Initially weight doesn't move (isometric) 3. When tension in spring (SEC) equals weight, movement begins (isotonic contraction) 4. Delay is longer for heavier weight C. DELAY in tension buildup due to SEC 1. Can measure movement of contractile components 2. QUICK STRETCH EXPT. a) Rapidly stretch muscle to take up slack in SEC b) Stimulate muscle c) Contractile components engage within 1-2 msec (1) This is called ACTIVE STATE (2) Tension of contractile components d) Without quick stretch whole muscle doesn't reach peak until 10-100 msec

11 Organismal Lec X 01/25/00 Tension During Quick Stretch "Active State"

(without stretch)

Tension

Time

3. Peak tension of muscle during twitch occurs at LOW POINT of ACTIVE STATE a) Ca is quickly sequestered after spike b) This terminates active state c) SEC delays tension buildup (1) much like capacitor (2) So in one twitch muscle only gets part of max. tension capability (3) If second spike arrives before Ca is sequestered, active state remains high (a) tension can get greater - More Ca++ → More Tension (b) temporal summation

High Frequency Single Twitch A.P.s

Low Frequency A.P.s Tension

Time

(4) Series of twitches → increase in tension until cross-bridges

12 Organismal Lec X 01/25/00 start to SLIP (5) At this point tension plateaus - TETANUS 4. Some arthropods can overcome SEC to produce rapidly accelerating movements a) Result is quick and strong movement b) More than what could be accomplished with conventional contraction

Muscle contraction

Isotonic Movement Tension or Movement

Time

c) Cannot eliminate SEC but can delay movement until plateau (tetanus) is attained

Delay Movement Take up SEC Rapid Accel. Tension or Movement

Time

d) Snapping shrimp (1) two flat disks act like wetted glass (2) hold dactyl up until max. tension is produced (a) SEC taken up (3) results in very rapidly accelerating and powerful movement VIII. Variation of tension via motor neurons control

13 Organismal Lec X 01/25/00 A. Vert. motor spike → spike in muscle (all-or-none) 1. One innervates relatively few muscle fibers (approx. 100 fibers) 2. Each motor neuron + the muscle fibers it innervates = MOTOR UNIT

Motor Neuron

Muscle Fibers

3. So there are many motor units in each muscle 4. Variation in intensity of contraction of whole muscle is due to recruitment of motor units a) More motor units → more tension 5. So level of contraction is controlled in CNS by which motor neurons are brought to threshold. B. Arthropods - One motor axon innervates most if not all muscle fibers 1. So few axons (motor units) per muscle (5-6) 2. But they are much more extensive 3. But motor spike → GRADED synaptic unit NOT all-or-none 4. So change degree of contraction by changing amount of transmitter released from motor neuron 5. Just like neuron - neuron synapse, increase in transmitter is due to a) summation b) facilitation 6. In either case these lead to greater depolarization 7. But here greater depolarization does not → more muscle spikes, rather it → greater contraction C. So considerable integration occurs at arthropod muscle junction 1. Facilitation and temporal summation 14 Organismal Lec X 01/25/00 2. With more than one excit. motor neuron - Spatial summation 3. Some neurons are FAST → twitch-like contractions 4. Some neurons are SLOW → slow powerful contractions with considerable facilitation 5. Also some inhibitory motor neurons D. Vertebrate Fiber types 1. Tonic – Slow, No twitch (rare in vertebrates) a) Postureal muscles of amphibians, reptiles and birds b) muscle spindles and extraocular muscles in mammals 2. Slow Twitch (type I), Slow Oxidative a) Mammalian postural muscle b) Properties that allow for Oxidative metabolism and hence slow rate of fatigue (1) large number of mitochondria (2) rich blood supply to bring lots of O2 (3) high concentration of myoglobin stores O2 (4) Often called red muscle 3. Fast Twitch oxidative (type IIa) Rapid, fatigues slowly a) Rapid powerful movements e.g. running muscles of legs and flight muscles of wild birds 4. Fast Twitch glycolytic (type IIb) Rapid, fatigues quickly a) Forearm, Domestic Avian breast muscle not used in flying b) Few mitochondria, therefore, depend on anerobic glycolisis to generate ATP IX. Specialized Muscle A. Insect flight muscle (fibrillar muscle) 1. Wingbeat of bees, wasps (hymenoptera), beetles (coleoptera) and bugs (hemiptera) can beat up to 1000 Hz. a) This is too fast for normal motor neurons 2. Neural input not 1:1 with muscle contraction 3. Neural inputs provide increase in Ca conc. - via depolarization 4. Muscle won't contract until stretched 5. Mechanics of THORACIC BOX accomplish this

15 Organismal Lec X 01/25/00 Dorsal Plate

Wing

Thoracic Wall

Elevator Muscle

Depressor Muscles

6. Elevators contract → pulls down on dorsal plate of thorax a) forces wings up b) elongates thorax c) stretches depressors 7. So depressors contract a) wings go down b) thorax balls up c) stretches elevators d) etc. 8. Wing articulation has pieces of chitin that are BISTABLE a) wings are either all the way up or down b) acts as a click stop (like a toy clicker or a light switch) 9. This assures that alternate muscle gets strong stretch when wing moves 10. Not all insects fly like this 11. Locusts for example have typical direct muscle arrangement X. A. Similar to B. Muscle cells shorter C. Connected to one another via intercalated disks D. Electrical properties 1. Intercalated disks provides electrical connections 2. Action potential spreads throughout entire muscle

16 Organismal Lec X 01/25/00 3. Some cardiac cells initiate Action Potentials 4. Duration of A.P. longer than axons and skeletal muscle a) As a result does not recover from refractory period until active state (Ca release) is over b) Prevents tetanic build up c) tetanus would interfere with heart rhythm E. Stretch affects strength of contraction as in skeletal muscle 1. longer sarcomere length → more tension up to a limit 2. cardiac muscle operates over shorter range 3. not stretched as much as skeleton stretches skeletal muscle 4. Contractility of cardiac muscle can be altered by nervous or endocrine inputs XI. A. Surrounds hollow internal organs 1. intestine 2. blood vessels (not capillaries) B. types 1. single-unit (unitary) a) units mechanically and electrically coupled to each other b) viseral organs 2. Multi-unit a) few gap junctions b) only small number of cells act as a unit c) found in (1) iris of eye (2) walls of larger blood vessels (3) airways of lung (4) hair follicles (piloerection muscles) 3. Contractile mechanism a) contains actin and myosin b) but not organized into sarcomeres c) Are in parallel arrangements crossing diagonally from side to side

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Dense Bodies Contraction

d) Myosin molecules are attatched to structures called dense bodies (1) equivalent to Z structures e) No limit to distance thick and thin filaments can slide relative to each other f) Adaptive for organs that must experience large volume changes 4. Excitation-Contraction Coupling a) Muscle membrane has Basic Electrical Rhythm (BER) b) Pacemaker activity c) May → A.P.s d) Autonomic N.S. and hormones can alter BER e) Single unit muscle influenced largely by BER - similar to cardiac rhthm f) Multi-unit muscle requires extrinsic input from ANS rather than from BER to contract - similar to skeletal muscle g) Sarcoplasmic Retic. not elaborated as in skeletal muscle h) Relies upon Ca++ influx from extracellular space i) is a Ca spike rather than a Na spike j) Ca++ enters cell and combines with (1) light chain of myosin and (2) k) Puts myosin head into activated state l) Under low levels of Ca++ activates a molecule called caldesmon m) Forms Latchbridges n) Keeps heads attatched under low energy

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