1.02 Physiology Trans - Muscle Physiology

(1)

Dr. KATHERINE MUNARRIZ |

Muscle Physiology

19, June, 2015 19, June, 2015

1.02

SKELETAL MUSCLE SKELETAL MUSCLE

The skeletal muscle is multinucleated, striated and moves The skeletal muscle is multinucleated, striated and moves voluntarily

voluntarily



Each muscle covered by an EPIMYSIUMEach muscle covered by an EPIMYSIUM



Each muscle is composed of FASCICLES which areEach muscle is composed of FASCICLES which are covered by the PERIMYSIUM

covered by the PERIMYSIUM



Each fascicle is composed of several MUSCLE FIBERSEach fascicle is composed of several MUSCLE FIBERS (cells) which are covered by an ENDOMYSIUM (cells) which are covered by an ENDOMYSIUM



A muscle fiber is composed of several MYOFIBRILSA muscle fiber is composed of several MYOFIBRILS which are covered by the SARCOPLASMIC

which are covered by the SARCOPLASMIC RETICULUM (SR) and invaginated by T-TUBULES RETICULUM (SR) and invaginated by T-TUBULES (transverse tubules)

(transverse tubules)



SARCOLEMMA is a thin membrane enclosing aSARCOLEMMA is a thin membrane enclosing a skeletal muscle fiber. Through this, the action skeletal muscle fiber. Through this, the action potential passes towards the T tubules. potential passes towards the T tubules.



The T tubules are extensions or invaginations of theThe T tubules are extensions or invaginations of the sarcolemma that brings the action potential rapidly sarcolemma that brings the action potential rapidly to the innermost part of the muscle.

to the innermost part of the muscle.



Myofibrils consist of SARCOMERES that contain theMyofibrils consist of SARCOMERES that contain the Actin (Thin Filament) and Myosin (Thick Filament) Actin (Thin Filament) and Myosin (Thick Filament)



SARCOPLASM is the intracellular fluid betweenSARCOPLASM is the intracellular fluid between myofibrils that contains large quantities of K, Mg and myofibrils that contains large quantities of K, Mg and PO4, plus multiple protein enzymes. Also present are PO4, plus multiple protein enzymes. Also present are tremendous numbers of mitochondria that lie

tremendous numbers of mitochondria that lie parallel to the myofibrils. These supply the parallel to the myofibrils. These supply the

contracting myofibrils with ATP. Mitochondria also contracting myofibrils with ATP. Mitochondria also store Ca++ that adds to intracytosolic Ca++

store Ca++ that adds to intracytosolic Ca++ duringduring depolarization.

depolarization. Parts of a myofibril Parts of a myofibril



Sarcomere - segment of myofibril between two ZSarcomere - segment of myofibril between two Z lines/disc

lines/disc



Z lineZ line – – bisects the I-band; attachment of the actin bisects the I-band; attachment of the actin filament

filament



I band (Isotropic)I band (Isotropic) – – contains only actin (thin) contains only actin (thin) filaments

filaments



H ZoneH Zone – – light are between the A-band contains only light are between the A-band contains only myosin (thick) filaments

myosin (thick) filaments



A band (Anisotropic)A band (Anisotropic) – – dark striation of the myofibril dark striation of the myofibril that contains both actin and myosin

that contains both actin and myosin



M lineM line – – bisects the H zone bisects the H zone

*In a normal contraction/ regular contraction,

*In a normal contraction/ regular contraction, it is theit is the H zoneH zone and I band which shorten.

and I band which shorten. *The

*The I band, A band and Z disc/ lineI band, A band and Z disc/ line give the skeletal muscles give the skeletal muscles its

its striatedstriated appearance.appearance. Muscle filaments Muscle filaments

 Thick Filament (Myosin)Thick Filament (Myosin) tethered to the Z-lines by a

tethered to the Z-lines by a cytoskeletalcytoskeletal protein called titin

protein called titin

composition: composition:

a. large protein that consists of six diff

a. large protein that consists of six diff erent polypeptideserent polypeptides b. one pair of large heavy chains

b. one pair of large heavy chains c. two pairs of light chain

c. two pairs of light chain



Thin Filament (Actin)Thin Filament (Actin)

formed by the aggregation of actin molecules formed by the aggregation of actin molecules (G-actin) into a two-stranded helical filament (F-(G-actin) actin) into a two-stranded helical filament (F-actin) Tropomyosin

Tropomyosin – – inhibits binding of myosin to actin inhibits binding of myosin to actin by coveringby covering the binding site

the binding site Troponin complex Troponin complex

a.

a. Troponin T -Has strong affinity Troponin T -Has strong affinity to tropomyosinto tropomyosin -Attaches the troponin complex to -Attaches the troponin complex to tropomyosin

tropomyosin

-No. 1 inhibitor of Cross-bridge formation -No. 1 inhibitor of Cross-bridge formation b.

b. Troponin I- Has strong affinity to actinTroponin I- Has strong affinity to actin

-Inhibits interaction of actin and myosin -Inhibits interaction of actin and myosin c.

c. Troponin C -CaTroponin C -Ca++++_{protein that once bound permits}_{protein that once bound permits} myosin and actin interaction by the myosin and actin interaction by the movement of tropomyosin, thereby movement of tropomyosin, thereby exposing the myosin binding sites. exposing the myosin binding sites. *A thin/actin filament is made-up of

*A thin/actin filament is made-up of the following proteins:the following proteins: actin globules, tropomyosin and troponin (T, I, and C). actin globules, tropomyosin and troponin (T, I, and C).

(2)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

SKELETAL MUSCLE CONTRACTION Neuromuscular Junction Transmission



SYNAPSE is the area between a nerve and a muscle cell



LOWER MOTOR NEURON (LMN) supplies the muscle cell and synapses with the SkM fiber

 SOMATIC NEURON – supplies the Skeletal muscle

 AUTONOMIC NEURON – supplies the Smooth muscles



END PLATE –the part of the muscle where Ach attaches to the receptor sites



ACETYLCHOLINE –the only neurotransmitter found in the NMJ



NEUROMUSCULAR JUNCTION (NMJ) -End Plate + Post Synaptic Axon Terminal



END PLATE POTENTIAL (EPP) –a localized non-propagated potential that could produce an AP in the muscle when threshold is reached

1. An Action Potential (AP) is received by a neuron and travels down the axon to the a xon terminal

2. The AP causes an influx of Na+ which causes a depolarization while an efflux of K+ will cause a repolarization. The repolarization causes the regeneration of the AP and the next depolarizing event occurs at the Node of R anvier and continues to the next until it reaches the axon terminal. Some Notes:

-Upper motor neuron- located in brain cortex -mostly excitatory (Na+ influx) -Interneuron- mostly inhibitory (K+ efflux; Cl- influx) -Lower Motor Neuron-found in spinal cord

-Axon Hillock- where action potential is generated.

3. The AP at the axon terminal allows the opening of thevoltage-gated Ca++ channels which causes an influx of Ca++

4. Ca++ entry triggers the release of Ach from the axon terminals

5. Ach diffuses from axon terminals to the synaptic cleft and attaches to the receptor sites at the motor end plate/sarcolemma of the muscle

6. The binding of the Ach to the receptors opens Ca ++ channels at the end plate and causes and influx of Ca++ and an efflux of K+, depolarizing the membrane (sarcolemma), producing the EPP.

7. EPP depolarizes the adjacent muscle cell plasma membrane to its threshold potential, generating an AP that propagates the muscle fiber surface

Nerve Cell Resting Membrane Potential (RMP): -70 mV Nerve Cell Threshold Potential: -55mV

Skeletal Muscle Cell RMP: -90mV

Skeletal Muscle Cell Threshold Potential: -75mV

8. The AP travels from the sarcolemma towards the T-tubules

9. From the T-tubules, the AP reaches the Ca ++ channel DHPR ( Dihydropyridine Receptor) and activates the RYR (Ryanodine Receptor) which releases Ca++ from the terminal cisternae of the Sarcoplasmic Reticulum (SR) into the myoplasm



T-tubules are extensions/invaginations of the Sarcolemma that extends into the muscle fiber, forming a close association with the two terminal cisternae of the SR



This association of the T-tubule with the terminal cisternae is called a triad



The T-tubule and the terminal cisternae are connected by bridging proteins called feet



These feet are the RYR through which the Ca ++ is released in response to an AP



At the T-tubule membrane, the RYR interacts with the DHPR which is an L-type voltage gated Ca++ channel with five subunits

(3)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02 

One of the subunits of the DHPR appears to be critical for the ability of the AP in the T-tubule to induce release of the Ca++ from the SR



However, influx of Ca++ into the cell through the DHPR is not needed for the ini tiation of Ca++ release from the SR



Instead, release of the Ca++ f rom the terminal cisternae of the SR is thought to result from a

conformational change in the DHPR as the AP passes down the T-tubule



This conformational change, by means of a protein-protein interaction, opens the RYR (like a mechanical opening of a door) and releases the Ca++ into the myoplasm

10. When the Ca++ is released, it binds to Troponin C which promotes the lateral movement of the Troponin-Tropomyosin complex, exposing the myosin-binding site on the actin filament

11. Immediately, myosin heads bind to the sites on the actin filament and contraction happens

12. The Ca++ that was previously bound to Troponin C is reabsorbed by the tubules of the SR

13. The reabsorption of the Ca++ causes the Tropomyosin to cover again the binding sites,

releasing the interaction of the myosin head and the actin filament

14. Ca++ uptake in to the SR (Ca++ ATPase) is due to the action of SERCA (Sarcoplasmic Endoplasmic

Reticulum Calcium ATPase)

15. From the tubules of the SR, the Ca++ is brought back to the terminal cisternae where it is stored



Calsequestrin is a low affinity Ca++ binding protein that helps accumulate Ca++ in the terminal cisternae

ECF Ca++: 10-3 mol/L

ICF Ca++: 10-8 mol/L resting; 10-5 mol/L contracted Ca++ is more concentrated in the ECF

Cross-Bridge Cycle

a. In the relaxed state, ATP is partially hydroyzed by Myosin

b. In the presence of elevated myoplasmic Ca ++, myosin binds to actin

c. Myosin releases ADP and phosphate ion. Hydroly sis of ATP is completed and causes a conformational change in the myosin molecule that pulls the actin filament toward the center of the sarcomere (powerstroke) and contraction occurs.

d. A new ATP binds to myosin and causes release of cross-bridge. Partial hydrolysis of the newly bound ATP recocks the myosin head, returning to the resting state. Myosin head is now ready to bind again and again.

The cycle continues until the SERCA pumps back C a++ into the SR. As Ca++ concentration falls, Ca ++ dissociates from Troponin C, and the troponin-tropomyosin complex moves and blocks the myosin binding site on the actin filament. If myoplasmic Ca++ is still elevated, the cycle repeats, if myoplasmic Ca++ is low, relaxation occurs.

Roles of ATP



Cross Bridge Cycling: 1 Cross bridge = 1 ATP



ATP causes both contraction (indirectly) and relaxation (directly)



Decreased production of ATP ->Rigor Mortis at death; In living persons, delayed contraction and relaxation

Mechanisms that Prolong Contraction Factors that prolong cytosolic Ca++

a. Increased frequency of AP

b. Defective Na+ inactivation: continued Na+ influx ->muscle membrane will be depolarized

->conformational change in DHPR leading to RYR activation ->hyperkalemic periodic paralysis c. Defective Ca++ RYR: continued Ca++ release

->Malignant Hyperthermia Mechanisms for Relaxation:

Relaxation occurs by decreasing the

cytosolic/intracellular Ca++ or by detaching the myosin head to actin.

1. Via SERCA (sarcoplasmic endoplasmic reticulum calcium ATPase):



Ca++ resequestered to SR due to Ca++ ATPase, an active pump



SERCA is the most abundant protein in the SR of skeletal muscles



Transports 2 Ca++ for each hydrolyzed ATP 2. Decreasing the action potentials



Decreases DHPR and RYRDecreased cytosolic Ca++

(4)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02 

Attachment of ATP to the myosin head 

detachment of myosin head to actin  eventually relaxes muscles

Phases of the Muscle Twitch 1. Latent phase



As action potential reaches sarcolemma and down the T-tubules and starts the excitation-contraction coupling



2 ms

2. Contraction phase



Cross-bridge formation (Actin-myosin interaction)



Includes isometric and isotonic phases of contraction



Maximum tension (TM) depends on the number of muscle fibers that are recruited during the

contraction



15 ms

3. Relaxation phase



Ca++ reuptake decreased tension in the sarcomere



25 ms Phases of Contraction

1. Isometric Phase



No isotonic phase of contraction



No change in muscle length.



Tension

TM is reached at end of the isometric phase of contraction, and is maintained thereafter;



Load (TL)

the load is not moved; there is simultaneous contractions (co-contraction) of agonist and antagonist muscles



TL<TM(-) shortening but (+) movement of load



TL=TM(-) shortening and movement of load 2. Isotonic Phase



Isometric phase + isotonic phase



(+) change in muscle length (most of the time, shortens)



Concentric contraction: shortening of the muscle during contraction



Eccentric contraction: lengthening of the muscle during contraction



Tension

TM is reached at end of the isometric phase of contraction, or during the isotonic phase



When TL TM, the muscle shortens and the load is moved



TL > TM (+) LENGTHENING and movement of load



TL =TM(-) shortening and movement of load Muscle Tension

Tension refers to the interaction of actin and myosin. 1. Active tension



Generated when the opposing actin filament is almost equal to myosin filament exerted during the cross-bridge formation.



How to increase the active tension?

Spatial summation: increase number of cross-bridges (length of actin-myosin overlap)

Temporal summation: increase number of action potentials by increasing UMN LMN

sarcolemma stimulation (frequency of stimulus) 2. Passive tension



Tension between connective tissues or cell elements



“Lo” (optimal length), which is between 2.0 – 2.2



m in both skeletal and cardiac muscle, and 90 – 110% of the original muscle length.



Lo = start of passive tension (refer to the picture below)



Change in passive tension is directly proportional to muscle length



Usually the tension measured before muscle contraction.



Refer to the picture below:

Clinical importance of providing passive tension after a n extensive exercise (i.e. cool-down/stretching)  Allows muscle to go back to its LO Increasing efficiency of muscle

length and avoids muscle pain induced after the exercise (delayed-onset muscle soreness/DOMS)

Relationships between…

MUSCLE TENSION AND MUSCLE LENGTH



LO = 2.0 - 2.2 μm for skeletal and cardiac muscles



Active tension: As stress increases, muscle length also increases up to LO. Beyond this point, contractile force (stress) decreases.

(5)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02 

Passive tension: When muscle is at rest, stretching of the muscle length initially increases stress slowly, and then more rapidly as the extent of stretch increases.

Length-Tension Relationship



Optimal length of sarcomere prior to

contraction = 2.0

–

2.2



m

initial length

# cross-bridges

tension in fibers

MUSCLE TENSION AND FREQUENCY OF STIMULATION



Dependent on motor unit activity.



Summation of muscle contractions Spatial summation

o



cross-bridges of muscle fibers or increasing the

tension twice as its original load Temporal summation (Tetanus)

o



number of action potentials or



frequency of

stimulation

o Results to prolonged cytosolic Ca++ increased

number of cross-bridges  increased active tension

MUSCLE TENSION AND VELOCITY OF SHORTENING or LENGTHENING



Increasing the load will increase the cross-bridges:

The Third Law of Newton: When a mass exerts a force on another mass, the second mass

simultaneously exerts a force equal in magnitude but opposite in direction to that of the first mass.



When all the muscle fibers in the muscle bundle have been recruited to carry the load  the tension

generated by that muscle bundle is maximal (see point B of the power-stress curve)



Yellow-box region: isotonic concentric contraction



Green-box region: isotonic eccentric contraction



Point C: isometric contraction (no change in muscle length) Poin t Load Tension Velocity of shortening /lengtheni ng Other notes: A No load Submaxim al Maximal No power since no distance was covered B Submaxim al Submaxim al Submaxima l Max power

C Maximal Maximal Zero

No power since work velocity is zero; Maximum tension D Supramax. Max. to decreasin g **Increasin g from point C/isometric phase (doesn’t Velocity of lengtheni ng

(6)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

mean that eccentric contractio n is faster than concentric)

Muscle Fiber Types

 Recruitment of muscle fibers (accdg. to Size Principle of Recruitment):



Simultaneous activation of muscle fibers done to increase force of contraction



Muscle fibers with lower thresholds are stimulated first



Weak stimulus: activates neurons with low threshold (small motor units at the level of UMN)



Strong stimulus: activates neurons with high threshold

 Types of fibers:

1. Type I (Slow-oxidative fibers)



Slow twitch



Uses aerobic respiration (consumes oxygen, glucose, fatty acids, and lastly the 30-32 ATPs)



Less fatigable; hence, good for prolonged activities



Recruited first than fast-twitch fibers since these fibers are small and are easily excited.



For mild-moderate intensity activities that requires control and endurance

2. Type II (Fast twitch)



May be Type IIa oxidative) or Type IIb (Fast-glycolytic – focus)



Type IIa (intermediate): uses aerobic respiration (consumes oxygen, glucose, fatty acids, and lastly the 30-32 ATPs)



Type IIb: uses anaerobic respiration (ADP and creatine phosphate/CrP)



More fatigable



Recruited later as more and more force i s needed since these fibers are large and more diffi cult to excite.



For high-intensity activity that entails great power.

Summary of basic classification of skeletal muscle fiber types

Muscle Tone



Muscle tone refers to the tautness of a muscle, even at rest.



Mechanisms for Muscle Tone:

At rest,type II afferents (sensory nerves at the muscle spindle) tonically send afferent

proprioceptive impulses towards the spinal cord where they synapse with the lower motor neurons (LMN).

1. The alpha MN synapses with the extrafusal muscle fibers, while the gamma MN synapses with the intrafusal muscle fibers, or the muscle spindles.

(7)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

2. The afferents synapse monosynaptically with the alpha MN, and polysynaptically with the gamma MN.

*More on this concept, in the Study Guide on the Autonomic Nervous System, where the myotatic / stretch reflexes will be discussed.

Muscles are arranged in antagonist pairs and groups. Asone muscle exerts a little contraction in response to the impulses passing thru the reflex arc, it stretches its antagonists, causing them to send proprioceptive sensory information back to the spinal cord. Thus, a normal state of involuntarily controlled contractions of various skeletal muscle fibers in different muscle groups occurs, which keeps all individual muscles in a state of partial contraction, and ready to contraction more forcefully if voluntary

commands are received from the cortical motor areas.

Muscle Fatigue



Prolonged and strong contraction of a muscle 

inability of the contractile and metabolic processes of the muscle fibers to continue supplying the same work output FATIGUE!



Mechanisms of (peripheral) muscle fatigue:

Failure of nerve impulses to release enough ACh

Depletion of ATP, glycogen, creatine PO4

Build-up of ADP inhibits CB cycling

Depletion of ICF K+_{or accumulation of ECF K}+



Release of Ca++_{ions from SR}





protons (



pH) changes protein conformation

CARDIAC MUSCLES



Cardiac muscle is STRIATED and INVOLUNTARY.



Some cardiac fibers are connected by intercalated disks.



Cardiac muscle is capable of self-excitation.



FASCIA ADHERENS and DESMOSOMES provide mechanical connection.



GAP JUNCTIONS in between cells provide electrical connection.

1. Excitation of cardiac muscle results from: a. Primarily by:

i. Pacemaker potentials

ii. Electrical coupling, or depolarization via gap junctions -these will result in depolarization of the ca rdiac muscle, and activate the DHPR. I n contrast to the skeletal muscle wherein DHPR mechanically changes the RYR to release Ca++ from the SR, activation of the DHPR in cardiac muscle fibers result in a small flux of Ca++ into the

sarcoplasm -> small increase in cytosolic Ca++ will open the

RYR channels (Ca++-induced Ca++ release from SR) -> large increase in cytosolic Ca++ -> cardiac muscle contraction. b. Modulation by:

-neuromuscular transmission, via autonomic nerves’ release of neurotransmitters.

2.Action Potential

a. Fast Response (happens in the atrial and ventricular cardiac cells and in the Purkinje fibers)

Phase 0: Rapid Na+ influx caused reversal of polarity from (-) to (+) depolarization.

Phase 1: K+ efflux causes an EARLY REPOLARIZATION. Phase 2: Ca++ influx maintains impulse (plateau) Phase 3: continuous K+ efflux makes the cell’s polarity become more (-) than the previous (+) it was (repolarization). Phase 4: Resting state achieved.

b.Slow Response (happens in the sinoatrial node and atrioventricular node via cardiac conduction system) Why does the duration of the action potential make tetanic contractions impossible in cardiac muscle fibers?

Cardiac muscle and skeletal muscle differ, however, in the level of intracellular [Ca++] attained after an action potential and hence in the number of actin-myosin interactions are high after an action potential. In cardiac muscle, the rise in intracellular Ca++ can be regulated, which affords the heart an important means of modulating the force of contraction without recruitment of more muscle cells or undergoing tetany. Recall that in the heart all the muscle cells are activated during a contraction, so recruiting more muscle cells is not an option. Moreover, tetany of cardiac muscle cells would prevent any pumping action and thus be fatal. Consequently, the heart relies on different means of increasing the force of contraction, including varying the amplitude of the intracellular Ca++ transient.

3.Contraction Events

What are the mechanisms for the increase in cytosolic Ca++ in cardiac muscle?

-influx through voltage-gated L-type Ca++ channel

-Ca++-induced Ca++ release (CICR) from the SR (DHPR -> Ca ++ bind with RYR

-through β-adrenergic agonists (activation of β-receptors -> activates adenylyl cyclase -> ^ cAMP -> phosphorylation -> ^ Ca++ in SR

4.Relaxation Events ↓ICF Ca++ through -Ca-ATPase/ SERCA -Ca-ATPase/ sarcolemma

-Ca++-Na+ antiporter (secondary active transport: 3Na in, 1Ca out)

(8)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

5.Muscle Tension ^muscle tension, contraction force ^cytosolic Ca++ - by β-agonists

^sensitivity of myofilaments to cytosolic Ca++ - ^ stretch by ^preload (Frank-Starling Mechanism)

*Phospholamban- protein which activates SERCA when there is no epinephrine or β-agonist present upon phosphorylation. SERCA- involve in muscle relaxation.

Β-1 agonists -> ^rate of contraction -> ^peak tension -> rate of relaxation

6.Summation of muscle contractions:

Spatial & temporal summation: seen on individual C ICR events

7. Isometric and isotonic phases of cardiac muscle contractions

a. Isometric phase= isovolumic contractions; (-) muscle shortening; ↑T ~ ↑ ventricular pressure

b. Isotonic phase= occurs during ejection; muscle shortening occurs here

9. Preload vs. Afterload of Cardiac Muscle

a. Preload= load on non-contracting ventricular or atrial muscle

-filling of blood in ventricles during diastole -PASSIVE TENSION

b.Afterload= load on contracting ventricular or atrial muscle. -ACTIVE TENSION

i. What constitutes the afterload on atrial muscle? On ventricular muscle?

Arterial pressure (will be increased by ^cross bridges -> hypertrophy) , aortic impedance to blood f low, ventricular volume

ii & iii. Anything that ^afterload -> ↓shortening of myocardial fibers during systole -> ↓systolic volume

There is only ONE PHYSIOLOGICAL MECHANISM for SkM, SmM, CM hypertrophy: ^ AFTERLOAD.

10. Muscle Fiber Type of Cardiac Muscle: Slow-twitch muscle fiber type

11. Energy Sources of cardiac muscles:

Approximately 70-90% of energy is normally derived form oxidative metabolism of fatty acids with abou 10-30% coming from other nutrients, especially lactate and glucose.

SMOOTH MUSCLES

Accdg. kay Doc, ang importanteng malaman ditto ay ang contraction-relaxation mechanisms at yung iba ay hindi masyado dahilsa discussion ng ANS pa ang mga ‘yun.

Excitation of smooth muscle results from:



Pacemaker potentials



Electrical coupling, or depolarization via gap junctions



Neuromuscular transmission, via autonomic nerves’ release of neurotransmitters (further discussed in the Study Guide and Lecture on the Autonomic Nervous System)



Hormone activation of receptors

*Signal Transduction mechanisms will be further discussed in the Study Guide for the Autonomic Nervous System.

(9)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

Contraction Events



Calcium ions bind to c almodulin, instead of troponin C.



MLCK phosphorylates the myosin light chains, and energizes the myosin head to bind with the a ctin filament (crossbridge).

Relaxation Events:

1. Dephosphorylation of light chains by myosin light-chain phosphatase (MLCP) to decrease intracellular Ca++

2. Stress-relaxation phenomenon



Ability to return to nearly its original f orce of contraction seconds/minutes after it has been elongated or stretched.

3. Reverse stress-relaxation phenomenon



Ability to return to nearly its original force of contraction seconds/minutes after it has been shortened.

Relaxation Events:

1. Ligand action



NE, AII, and ET-1 alpha-receptor

stimulation of Gq PL-C PIP2 + IP3

increase Ca++ 2. DHPR CICR



Not as prominent as in cardiac muscle

Must-know concepts (Summary):

I talked to Dra. Munarriz at sabi niya ay halos lahat ng nasa table raw na ito ang lalabas sa exam. (Yanna)

SKELETAL CARDIAC SMOOTH

Nuclei Multinucleated ; Subsarcolemm al (peripheral) 1-2 nuclei; cytoplasmic (central) Single nucleus; cytoplasmic (central)

DHPR and RYR DHPR opens channels of RYR to release Ca++ from SR The DHPR (L-type) contains the Ca++ channel to release Ca++ (-) DHPR and RYR

Ca++ ions are released through the

(10)

Dr. MUNARRIZ |

Muscle Physiology

PHYSIOLOGY

1.02

activation of IP3 receptor, the RYR of striated muscles Regulatory proteins for muscle contraction (for Ca++ binding)

Troponin C Troponin C Calmodulin

Ca++_{Source (SR} or ECF, or both?) SR Both Both (sometimes with mitochondria) Events of Contraction Action potential T-tubules Ca++ from SR  inc. Ca++ Action potential opens voltage-gated Ca++ Hormones and transmitters open IP3-gated Ca++ in SR Influx of Ca++ during plateau of action potential -> calmodulin Activation of MLCK phosphorylates regulatory MLC Inc Ca++ Cross-bridging Events of Relaxation Via SERCA, decreasing action potentials, or myosin ATPase Reaccumulatio n of Ca++ by SR via Ca++ ATPase Stress-Relaxation mechanism, Dephosphoryla tion of light chains by myosin light-chain phosphatase (MLCP) Main Sources of Energy (glucose or fatty acids, or both?)

Both Fatty acids

Motor neuron (somatic or autonomic, or

both?)

Somatic Autonomic Autonomic

Neurotransmit ters (for cardiac, smooth) ACh Epinephrine Several neurotransmitt ers depending on the location of muscle Signal transduction mechanisms (for cardiac, smooth) cAMP for adenyl cyclase inhibitition (via beta-2 and alpha-2 receptors) *See picture of smooth muscle sig. trans. cGMP for smooth muscle relaxation; cAMP for glycogen synthesis Mechanisms that increase ICF Ca++ Depolarization of T-tubules to activate DHPR and RYR Increase heart rate; Sympathetic stimulation; (+) of cardiac glycosides Ligand action; and DHPR activating CICR Mechanisms that decrease ICF Ca++ Reuptake of Ca++ by the SR  Ca++ released from troponin C low cross-bridge cycling Parasympatheti c stimutation (Ach) via muscarinic receptors Mechanisms or Contraction Force Summation, recruitment, and preload are varied to varying force Contractility and preload are varied to varying force; Changing contractility affects speed of contraction Recruitment, summation, preload, and contractility are varied to varying force. Formation of latch-bridges reduces speed of contractility. Reminders:

For the First Long Quiz, 40 questions regarding muscle physiology

 15 questions about each specific concept ( with asterisk) in the table below

 15 questions about the concepts outlined or discussed above

 10 questions for the specific differences between skeletal, cardiac and smooth muscle

Legend: ^- increase

“If you don’t go after what you want, you’ll never have it. If you don’t ask, the answer is always no. If you don’t step forward, you’re always in the same place.” ( Nora Robert