Dr. Josefina Ramos-FrancoDept. Molecular Biophysics and PhysiologyJelke, rm.1255cPhone : 2-6433Email : jrfranco@rush.edu

Skeletal Muscle

READINGBoron & Boulpaep Book: Chapter 9 pages 230-254

LEARNING OBJECTIVES1. Describe 3 types of muscle and give examples of each and their

function.2. Draw a skeletal muscle sarcomere, label each part and describe

each parts functional significance.3. Diagram the chemical and mechanical steps in the crossbridge cycle.4. Draw the thick and thin filament, label each part and describe each

parts functional significance.5. Describe the process of neuromuscular transmission.6. Explain the roles of the ryanodine receptor and dihydropyridine

receptor in skeletal muscle excitation-contraction coupling.7. Describe the phenomena of skeletal muscle twitch, summation and

tetanus.8. Draw a length tension diagram and explain why the shapes of the

passive and active curves.9. Describe the differences between fast and slow twitch muscle fibers.10. Explain the role creatine phosphate in replenishing ATP supplies

and define the term oxygen debt.

Three Types of Muscles1. skeletal muscle2. cardiac muscle3. smooth muscle

Skeletal Muscle :1. Voluntary Control2. Striated Appearance3. Large, independently operating cells4. Usually relaxed until needed

(attached to bones, involved in locomotion)

Skeletal musclecell segment,note striations

EM image ofcell interior

EM image ofcell interior, intracellularmembranesstained dark

* Huge size * Multinucleated

. B&L Fig. 17.1

Comparison other Muscle Types(skeletal vs. cardiac/smooth)

Cardiac Muscle : (only found in heart)1. Involuntary Control2. Striated Appearance3. Cells 100x smaller than in skeletal muscle4. Neighboring cells operate as unit

(cells electrically & physically coupled)

Smooth Muscle : (wall of hollow organs)1. Involuntary Control2. Smooth Appearance (not striated)3. Small cells4. Many structure & regulatory variations

Skeletal Muscle :1. Voluntary Control2. Striated Appearance3. Large, independently operating cells4. Usually relaxed until needed

(attached to bones, involved in locomotion)

Skeletal MuscleNeuromuscular Transmission

Neuromuscular Transmission : 1. Chemical Synapse b/w motor neuron and muscle2. Neurotransmitter = Acetylcholine (Ach)3. Receptor = nicotinic AchR (nAchR)4. nAchR is cation channel, open upon Ach binding

(its opening depolarizes muscle endplate)

. B&B Fig. 8.4

Morphology & Membrane Organizationof Skeletal Muscle

Notable Features : 1. Sarcomere = contractile unit, overlapping proteins2. Transverse tubules (T-tubes) = surface membrane

invaginations continuous with surface3. Sarcoplasmic Reticulum (SR) = intracellular organelle,

specialized to store and release calcium4. Triad = junction of one T-tube and two SR elements

(T-SR gap is ~ 100; gap spanned by proteindense structures called feet)

. B&B Fig. 9.8a

ExcitationContraction (EC) Coupling

Steps of EC coupling : 1. Surface membrane excitation (AP)2. T-tube depolarization (by AP) triggers SR Ca release3. Ca activates contractile apparatus, activates contraction4. Contractile apparatus active until Ca removed5. Ca removed by ATP driven SR Ca pump, cell relaxes

SarcoplasmicReticulum

ContractileApparatus

1) MembraneExcitation

2) CalciumRelease

3) Calcium ActivatesContractile Apparatus

4) Removal of Calcium Turns-Off Contraction

5) Calcium Uptake

RELAXATION CONTRACTION

Ca2+

Ca2+Ca2+

ATP

ATP

surface

T-tube

( SR )

AP

The Mechanism that TriggersSR Ca Release

Notable Features : 1. DHPR = dihydropyridine receptor, T-tube voltage sensor2. RyR = Ryanodine receptor, SR Ca release channel, foot3. DHPR and RyR physically linked together4. Vm-induced DHPR conformation change conveyed

to RyR causing it to open, releasing Ca from SR

Skeletal SR Ca Release Trigger Mechanism : Physical functional link between DHPR and RyR

. B&B Fig. 9.9

Sarcomere Structure

SLIDING FILAMENT THEORY

. B&B Fig. 9.4

Thick Filament Structure

Notable Features : 1. Thick Filament = 300-400 myosin molecules2. Each myosin has globular head and filamentous tail3. Myosin tails align side-by-side 4. Globular head extend outward5. Myosin globular head form crossbridges between

thick and thin filaments

Individual Myosin

Molecules

ThickFilament

globular headfilamentous tail

. B&B Fig. 9.4

Thin Filament Structure

Notable Features : 1. Thin Filament = Action + Tropomysin + Troponin2. Filament core = double-stranded actin helix3. Tropomysin lies along actin helix groove4. Troponin attached to end of each tropomysin5. Troponin had 3 subunits (TN-I, TN-C, TN-T)

Thin Filament Ca Switch : 1. Ca binds to TN-C2. TN-C conformation change moves tropomyosin3. Exposes myosin binding sites on actin

Individual Actin

Monomers ThinFilament

. B&B Fig. 9.5

Steps in Crossbridge Cycle : ATP binds and myosin head detaches ATP hydrolysis energizes the unattached myosin head Myosin head unattached and energized (cocked) Energized (cocked) myosin head binds to actin ADP & Pi are released and power stroke occurs Thick and thin filament are pulled past each other Spent myosin head remains attached until ATP binds

Crossbridge Cycle

. B&B Fig. 9.7

Definitions : 1. Isometric = muscle contracts with overall length constant2. Isotonic = muscle shortens at constant load

Muscle Length-Tension Relationship

Notable Features : 1. Passive + Active = Total Tension2. Passive element due to inherent muscle elasticity3. Active element due to sarcomere shortening4. Active length-tension curve is bell-shaped5. Bell-shape is a consequence of sarcomere structure

. B&B Fig. 9.12

Definitions : 1. Twitch = transient contraction elicited by single AP2. Summation = super-twitch tension elicited by a second

AP occurring before previous twitch ends3. Tetanus = maximum tension at very high AP frequency

Twitch, Summation and Tetanus

AP = 2 ms longTwitch = 50-150 ms

. B&B Fig. 9.14

Definitions : 1. Fast Twitch = large fibers, fast contraction, fatigue easy

fewer mitochondria, rely on glycolysis2. Slow Twitch = small fibers, slow contraction, fatigue

resistent, more mitochondria, rely onoxidative phosphorylation, red color

Fast and Slow Twitch Muscle Fibers

Motor Unit = motor neuron + all muscle fiber it innervates

1. Motor units vary in size (3 to 300 muscle fibers)2. Motor units are recruited small to large, asynchronously3. Fibers in motor unit are either all fast or all slow

The Motor Unit. B&B Fig. 9.15

Lots of ATP needed for, 1) crossbridge cycling2) SR Ca pumping3) maintain Na/K gradients (Na-K pumping)

Skeletal Muscle Energy Consumption

Creatine Phosphate System : rapidly converts ADP to ATP

Oxygen Debt : excess oxygen consumption after vigorousexercise to replenish creatine phoshpateATP levels.

Clinical Notes

Malignant Hyperthermia:

An inherited disease manifested by muscle convulsions resulting in an uncontrollable rise of body temperature.

One trigger of this syndrome is general anesthetics (e.g. halothane). Treated by administration of the muscle relaxant dandrolene.

Disease is linked to a mutation in the skeletal RyR (making channel hyperactive).

Muscular Dystrophies:

A genetic family of diseases that typically occur in childhood. Some are manifested by progressive muscle degeneration and weakness, followed by loss of heart and lung function.

These diseases are linked to a group of proteins that form a dystrophin-glycoprotein complex important in maintaining skeletal muscle structural integrity (e.g. absence of dystrophin from skeletal muscle results in Duchenne Muscular Dystrophy).

Clinical Notes