Lecture 1 Physiology of Skeletal Muscle by Dr. Roomi

8/13/2019 Lecture 1 Physiology of Skeletal Muscle by Dr. Roomi

1/37

SKELETAL MUSCLE PHYSIOLOGY

Lecture#1

By

Dr. Mudassar Ali Roomi (MBBS, M. Phil)

Assistant Professor Physiology


2/37

Muscle Tissue

Skeletal Muscle

Cardiac Muscle

Smooth Muscle


3/37

Skeletal Muscle

Long cylindrical cells

Many nuclei per cell

Striated

Voluntary

Rapid contractions


4/37

Cardiac Muscle

Branching cells

One or two nuclei per cell

Striated

Involuntary

Medium speed contractions


5/37

Smooth Muscle

Fusiform cells

One nucleus per cell

Nonstriated

Involuntary

Slow, wave-like contractions


6/37


7/37

Arrangement of Thick and Thin Filaments in

Sarcomeres

The sarcomereis the basic

contractile unit, and it is

delineated by the Z disks.

Each sarcomere contains a full A

band in the center and one half of

two I bands on either side of the

A band.

The A bandsare located in the

center of the sarcomere and

contain the thick (myosin)

filaments, which appear dark

when viewed under polarized

light. Thick and thin filaments

may overlap in the A band; these

areas of overlap are potential

sites of cross-bridge formation.


8/37

Arrangement of Thick and Thin

Filaments in Sarcomeres (cont..)

The I bandsare located on either side of the A

band and appear light when viewed under

polarized light. They contain the thin (actin)

filaments, intermediate filamentous proteins,

and Z disks. They have no thick filaments.

The Z disksare darkly staining structures thatrun down the middle of each I band, delineating

the ends of each sarcomere.

The bare zone (H-zone)is located in the center

of each sarcomere. There are no thin filaments

in the bare zone; thus, there can be no overlap

of thick and thin filaments or cross-bridgeformation in this region.

The M linebisects the bare zone and contains

darkly staining proteins that link the central

portions of the thick filaments together


9/37

THICK AND THIN FILAMENTS

From surface of thickfilamentsprojectionsarisecross-bridges.

In centre of sarcomere,

thick filaments have noprojections (H zone).

The thin & thick filamentscontain contractile proteins:

The thick filaments contain

myosinprotein. The thinfilaments contain

actin, tropomyosin &troponinproteins.


10/37

Myosin protein: in thick filaments

In 1 thick filament200myosin molecules.

Molecular wt. of eachmyosin molecule = 480,000.

Each myosin molecule has 6polypeptide chains: 2 heavychains & 4 light chains.

2 heavy chains are coiledtogetherdouble helix.

At 1 end two heavy chainsare foldedhead portion.In head portion4 lightchains.


11/37

Myosin protein: in thick filaments (cont)

3 parts of myosin molecule:

Head

Arm / Neck

Body / Tail

There are 2 points in myosinmolecule at which molecule ishighly flexibleHINGES:

i) Between head & arm / neck

ii) Between arm & body / tail

Tail/body is present in thickfilaments.

Arm & head protrude out fromsurface of filament as cross bridges.


12/37

Myosin protein: in thick filaments (cont)

Cross bridges are absent in

centre.

In the centre of filament is tail

only, while cross bridges areformed by arm & head at

periphery as cross bridges.

In myosin head there are 2important sites:

Actin binding site.

Catalytic site.


13/37

Thin filaments

3 contractile proteinsare present

here:

1) ACTIN: Consist of 2 F-actin

strands. Each strand consist of

polymerized G actin molecules. Attached to each G actin

molecule is a molecule of ATP, &

point of attachment isactive

site on actin strand.

Active sites are present at every2.7 nm.

Each G actin has molecular wt.

42,000.


14/37

Thin filaments (cont)

2) TROPOMYOSIN:

Consist of 2 strands, with 70,000

molecular wt.

Tropomyosin strands at rest

physically cover active sites onactin filaments.

3) TROPONIN:

Attached to tropomyosin at

intervals.

It has 3 components: Troponin C, Troponin T, Troponin

I.

Molecular wt. 18,00035,000.


15/37

Thin filaments (cont)

Troponin CAffinity for calcium ions.

Troponin TAffinity for tropomyosin.(through which troponin complex isattached to tropomyosin)

Troponin IAffinity for actin strands.

It is the bond between troponin I &Actin, which keeps tropomyosin strandsin such a position that these physicallycover active sites of actin filaments.

During muscle contractionthis bondis broken.

Tropomyosin-troponin complex =relaxing protein(keeps muscle relaxed

by covering physically the active sites).


16/37

Components of Troponin

(C,T,I)


17/37


18/37

Important questions

1. Explain the molecular mechanism of muscle

contraction/Explain walk-along theory of muscle

contraction/ Explain sliding filament model of

muscle contraction2. What do you know about sarcotubular system and

its function?

3. What is the concept of excitation-contraction

coupling?

4. Enlist the histologic changes occurring in sarcomere

during muscle contraction.


19/37

Molecular Mechanism of skeletal muscle

contraction:

Muscle is first excited ordepolarized and then contratcs(EXCITATION-CONTRACTIONCOUPLING).

Action potential enters deep into

muscle fiber from T-Tubulesaround which are terminalcisternae.

So depolarization spreads from TTubulesterminal cisternae.

Membrane of terminal cisternaeis depolarizedopening ofvoltage gated calcium channelscalcium ions move out of theterminal cisternae.


20/37

Sarcotubular system


21/37

When it is in sarcoplasm, calcium is utilized by

troponin C to initiate muscle contraction

(excitation-contraction coupling).

4 calcium ions can bind with 1 molecule of

troponin Cit breaks the bond between

troponin I & Actintropomyosin strands

become loosethey reach a deeper positionactive sites on actin are uncovered.


22/37

Muscle contraction involves power strokes.

Before contraction, a molecule of ATP becomesattached to myosin head.

It is hydrolyzed to ADP to liberate energystored inmyosin head.

When active site is uncoveredmyosin head bindswith active site on actin.

With stored energy, there is power stroke. At hinges, myosin molecule moves & carries along

actin / thin filaments.


23/37


24/37

With energy of 2ndmolecule of ATP,it detaches & move back to originalposition2ndpower strokeaseries of power strokesslidingof actin over myosin so that power

stroke is towards centre ofsarcomereshortening ofsarcomere or contraction ofmuscle.

Each cross bridge operates

independently.

Greater the number of crossbridges coming in contact withmyosin headgreater is force ofcontraction.

When muscle is stretchedmorenumber of cross bridges attachedwith actin filamentsincreasedcontraction force.


25/37

Binding Site Tropomyosin

Troponin


26/37

Myosin


27/37


28/37


29/37

FRANK-STARLING LAW:

Greater the initial length ofmuscle, greater is force ofcontraction up to certainlimits.

Cardiac muscle also obeysthis law( increased venousreturnincreased lengthof cardiac muscle

increased fillingincreasedemptying by contraction ofventricle.

Applicable on skeletal andcardiac muscle.


30/37

Transverse Tubules and the Sarcoplasmic

Reticulum (sarcotubular system)

d b


31/37

Contraction is initiated bycalcium ions.

As long as calcium ion issufficient in sarcoplasm

muscle contraction continues. Normally in the wall of

longitudinal tubule, there iscalcium pump.

Calcium is released fromterminal cisternae but ispumped back by calciumpump & when calcium is lowin sarcoplasmmusclerelaxes.

So, even to produce musclerelaxation, we need ATPbecause calcium pump needsATP.


32/37


33/37

Sarcomere Partially Contracted


34/37

Sarcomere Completely Contracted


35/37

SLIDING FILAMENT MODEL OF MUSCLE CONTRACTION


36/37

Histological changes in sarcomere during muscle

contraction:

RELAXED MUSCLE:

2-2.5 m length of sarcomere.

AFTER CONTRACTION:

1-1.5 m length of sarcomere.

Length of A band constant.

Length of I band decreases. Z Membranes become closer.

H zone decreases / disappear

Sliding of thin over thickfilaments.

Length of individual filamentsremain the same.


37/37

Lecture 1 Physiology of Skeletal Muscle by Dr. Roomi

Documents