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Skeletal Muscle

EXT16

Dr Gareth Hathway

Revision Sessions
MPharm students have a timetabled revision surgery Dr Smith and myself are organising a VOLUNTARY revision session for Medics in association with Pins and Needles (UoN Anaesthetics Society) to take place in the New Year We need some idea of numbers and will give you details of how and where to sign up next week www.pins-needles.co.uk if you are really keen you can e-mail pinsandneedles.medics@googlemail.com and express your interest

Lecture objectives Describe the structure of skeletal muscle List the factors which affect muscle force generation Describe the metabolic requirements for contraction of muscle Explain the different functional properties and metabolic requirements of fast and slow muscle fibers

What purpose does skeletal muscle serve ?

Voluntary movement Under the control of the somatic nervous system Limb movement, torso, lips, tongue, eye muscles, head and neck

skeletal: maintain posture and move limbs

cardiac: heart

smooth: lines blood vessels and hollow organs

Skeletal muscle muscle = bundles (fasciculi) of fibers muscle fiber = long cylindrical multinucleate cell
Taken from Pocock and Richards 3rd Edition

30cm length 10-100m diameter

Muscle fibers made up of myofibrils 1um in diameter Composed of repeating units called sarcomeres Sarcomeres are the fundamental contractile unit of skeletal and cardiac muscle

myofibril

sarcoplasmic reticulim

Cell membrane

T-Tubules

Muscle contraction: interaction of actin and myosin in each sarcomere


sarcomere

Z A I A

2 m

How does a muscle contract?

Action potential required Ca2+ levels in the muscle cell must increase

SLIDING-FILAMENT THEORY OF CONTRACTION actin myosin actin

SLIDING-FILAMENT THEORY OF CONTRACTION

+ Ca2+

AP

epp muscle ACh-R

+ Na

AP

VOC (Na)
ATP-Ca pump

T tubule

Ca2+
VOC (Ca)

sarcoplasmic reticulum

CONTRACTION

Ca2+

Flow diagram to illustrate Sequence of events that leads To muscle contraction


(taken from Pocock and Richards)

Molecular events which allow actin and myosin to slide past each other
(from Pocock and Richards)

What prevents a muscle continuously contracting?

If actin and mysosin are mixed in a test tube they form a gel Add ATP and this contracts In muscle two other molecules, troponin and tropomyosin interact with actin to prevent it interacting with myosin Elevating Ca2+ in the muscle allows actin and myosin to interact

http://www.youtube.com/watch?v=H4mFWxaeMQo

http:// www.youtube.com/watch?v=Vlchs4omFDM&feature=re

Muscle Metabolism

The energy for contraction is derived from ATP This is derived from the oxidative metabolism of glucose and fats However blood flow through a muscle during contraction is intermittent

Muscle metabolism

resting

creatine kinase

creatine phosphate + ADP + H+

creatine + ATP

Energy metabolism in muscle fibers glycolysis 2 ATP


pyruvate acetyl CoA

TCA cycle
= citric acid cycle = Krebs cycle NADH

oxidative phosphorylation 36 ATP

electron transport chain (mitochondria)

types of skeletal muscle fiber contractile properties


I slow twitch red contraction strength fatiguability fiber diameter recruitment order twitch contraction weak resistant small early long (58-130ms) IIA fast twitch red intermediate resistant medium mid short (30-55ms) IIB fast twitch white strong fatuigable large late short (20-47ms)

types of skeletal muscle fiber metabolic properties


I slow twitch red IIA fast twitch red IIB fast twitch white glycolytic

metabolism oxidative oxidative (ATP source) phosphorylation phosphorylation #mitochondria high blood supply (capillaries) myosin ATPase myoglobin large very high large

low small

low high

high high

high low

Fiber composition of skeletal muscles


e.g. distribution of fibers types in rat ankle extensor muscles

100

% of fibers

75 50 25 0 GASTROCNEMIUS SOLEUS

slow twitch red fast twitch red fast twitch white

Armstrong and Laughlin (1985)

Muscle fatigue: fast twitch fibers glycolytic pathway: anaerobic respiration glycogen

glucose

pyruvate

lactic acid

ability to develop tension impaired pain (cramp, stitch)

Case history A 24 year old man presented with a ten year history of muscle cramps, mostly noticeable after exertion. Whilst at school he noticed severe cramps during cross country runs but if he kept going he could run through the pain. On one occasion after a two-mile race he had felt unwell and noticed that his urine was very dark.

What is the most likely diagnosis?

cramp myasthenia gravis McArdles disease motor neurone disease multiple sclerosis

What is the most likely diagnosis?

cramp myasthenia gravis McArdles disease motor neurone disease multiple sclerosis

McArdles disease glycogen storage disease = muscle phosphorylase deficiency inability to convert glycogen to glucose energy shortage within the muscle during anaerobic exercise Rhabdomyolysis muscle breakdown red/brown urine kidney damage treatment: lifestyle+diet

motor unit
the group of muscle fibers innervated by a single spinal motor neuron
upper motor neuron

lower (spinal) motor neuron

motor unit
innervation ratio varies: eye muscle 1 motor neuron = 3-6 fibers gastrocnemius (calf) 1 motor neuron = 2000 fibers

all muscle fibers in a motor unit are of the same type

recruitment of motor units

development of muscle tension is smooth and progressive motor neurons recruited progressively by CNS motor units activated at different times most muscles contain both fast and slow fibers

Time course of contraction force

fast twitch

AP

frequency of stimulation

single stimulus
AP

fused tetanus

isometric contraction force generated but muscle does NOT shorten ie load prevents contraction (velocity = 0) isotonic contraction force generated when muscle contracts power = force x velocity maximum power occurs at ~35% maximum velocity

two kinds of lower motor neuron spinal motor neurons innervate extrafusal muscle fibers - responsible for contraction

spinal motor neurons innervate intrafusal muscle fibers in muscle spindles - responsible for maintaining sensitivity of spindles (stretch receptors)

muscle spindles lie amongst extrafusal fibres They monitor muscle length They are innervated by both sensory and motor fibres

Stretch receptors

muscle spindle organ low threshold proprioception motor control Ia and II afferents

Golgi tendon organ high threshold - protect from damage Ib afferents

Golgi tendon organs lie in the tendon

Protective- monitor muscle tension

Summary Skeletal muscle is controlled via the somatic nervous system Use of these muscles is under voluntary control Muscle are composed of fibres which in turn are composed of myofibrils which in turn are composed of sarcomeres Fibers contract in response to an action potential and an elevation in [Ca2+ ]i