Muscles

Striated Cardiac Smooth

Excitability and contractibility

animations

• http://www.dnatube.com/video/4875/Physiology-of-muscle-contraction-and-relaxation

• http://www.dnatube.com/video/1306/Role-of-myosin-crossbridge-in-the-contraction-of-muscle

• http://www.dnatube.com/video/1952/Sliding-filament-causes-contraction-of-muscle

• http://www.dnatube.com/video/4154/Cellular-mechanism-of-muscular-contraction

Striated muscle – sarcomere

Striated muscle – sliding of contractile elements

Striated muscle – motor unit

Striated muscle – neuromuscular junction

Striated muscle – myography, tetanus

Muscle contraction •Twitch•Summation•Superposition

Tetanus•Smooth - multiple summation•Undulating – multiple superposition

Muscle strength

• Muscle strength depends on the number of motor units recruited

• Strength depends only on cross-sectional area 20 – 100 N per sq.cm Muscle cells cannot divide. Thickening is formed by duplication of myofibrils.

• Muscle strenght is influenced

– genetically– hormonally – testosterone,

anabolics

Muscle strength – tension/length curve, isometric and isotonic

contraction

Sources of energy for muscle contraction

• ATP – maintains contraction for 1 to 2 seconds• phosphocreatine – 5 times as great as ATP,

sufficient for 7-8 s contraction• Anaerobic Glycolysis

– Enzymatic breakdown of the glucose to pyruvate and lactate liberates energy that is used to convert ADP to ATP, glycolysis can sustain contraction for about 1 min

– Twofold importance of glycolysis• Reactions occurs in the absence of oxygen (muscle

contraction can be sustained for a short time when oxygen is not available)

• The rate of formation of ATP is 2.5 times as rapid as ATP formation with oxygen

• Oxidative metabolism – the final source of energy– 95% of all energy used by the muscle

Function of ATP

ATP is necessary for• Muscle contraction – detachment of the head

of myosin from the actin• Function of Na+/K+ pump• Function of Ca++ pumpPhysiological depletion of sources of ATP

(reversible) – contracture, spasm, crampIrreversible loss of all ATP – rigor mortis

– Lack of energy for the separation of cross-bridges– Rigor is faster after muscle fatigue and exhaustion– Muscles remain in rigor until muscle proteins are

destroyed by autolysis (15-25 hours)

Muscle fatigue• Acute (recovery - within 24 hours) and chronic

(may be followed by a complete exhaustion)• Decrease force of muscle contraction• Fatigue

– in the neuromuscular junction• Accumulation of extracellular K+ may lead to a disturbance

in depolarization, reduction of the amplitude of the action potential and conduction velocity

– decreasing amounts of muscle glycogen– Accumulation of lactate – lower pH, increase of K+,

stimulation of the free nervous endings – pain, edemas

– exhaustion of ATP

Striated muscle – twitch = types of muscles

TYPE I - SLOW TWITCH   Tonic muscles (darker:  red) - Leg muscles

TYPE II - (IIa & IIx) FAST TWITCH   Tetanic muscles (paler: white) - Pectoral muscles

longer contraction times (100-110 msec) shorter contraction times (50 msec)

contain myoglobin (red) no myoglobin (white)

continuous use muscles - prolonged performance    for endurance performance ( marathoners)

one time use muscles - brief performances     for power & speed (sprinters) 

marathoner: 80% type I   &   20% type II sprinter: 20% type I  &  80% type II 

best in long slow sustained contractions best in rapid (short) contractions 

not easily fatigued easily fatigued

more capillary beds, greater VO2 max  less capillary beds

smaller in size larger in size

lower glycogen content higher glycogen content

poor anaerobic glycolysis*  predominantly anaerobic glycolysis

    easily converts glycogen to lactate  wo O2

*  predominant aerobic enzymes & metabolism some aerobic capacity

higher fat content lower fat content 

more mitochondria - Beta Oxidation high fewer mitochondria- Beta Oxidation low

poorly formed sarcoplasmic reticulum well formed sacroplasmic reticulum

slower release of Ca = slower contractions quick release of Ca = rapid contractions 

tropinin has lower affinity for Ca troponin - higher affinity for Ca

Muscle pain

During exercise • Ischemic, hypoxic,

accumulation of metabolites, pH

• Fast in, fast out• Difficult to localize (muscle,

bone, tendom, joint)• Referred pain (viscero somatic

hyperalgesia)

After exercise • Dull ache when moving

or being palpated• Begins in 1-3 days and

lasts for one week• Maximal isometric

strength is not impaired• Does not correlate with

muscle edema, plasma CK, inflammation markers

Drugs that modify neuromuscular junction

Botulinum toxin prevents acetylcholine release – spasms (torticolis)

Methacholine, carbachol and nicotine – the same effect as Ach – not destroyed by acetylcholinesterase – long action – Ophtalmology (glaucoma)

Muscle relaxants – general anesthesia – muscle relaxation.

Curare (D-tubocurarine) blocks acetylcholine receptors w/o depol

Succinylcholine is a depolarizing blocker

Anticholinesterase drugs, neostigmine and physostigmine – reversible inactivation of acetylcholinesterase – accumulaiton of Ach – myasthenia gravis

Organophosphate – chemical weapons – irreversible inactivation of acetylcholinesterase – cramps, respiratory distress, sweating and convulsions.

Dandrolen blocks Ca realease from SR – malignant hypetermia

Smooth muscle - structure

actin and myosin

no troponin, calmodulin instead

Dense bodies – analog of Z-lines – attachment of actin filaments

Actin – long filaments, 15 times as myosin

• Contraction 30 times slower than that of sceletal muscle• constant power during contraction (isotonic line longer, since some contractile units have optimal overlapping of A&M at one length of the muscle and others at other length)

Types of smooth muscles• Multiunite

– discrete smooth muscle– single nerve ending– The ciliary muscle of the eye

(parasympathetic control)– The piloerector muscles

(sympathetic control)• Single-unit (visceral)

– Hundreds to millions contract together – syncythial

– gap junction – ions can flow freely

– gut, bile ducts, ureters, uterus, vessels

Contraction of smooth muscle

• Initiating event in smooth muscle contraction is an increase in intracelullar Ca2+ ions cause by:– Nerve stimulation– Stretch of the fiber– Hormonal stimulation– Changes in the chemical environment of the fiber

• Strength of contraction depends on extracellular Ca2+

• Removal of Ca2+ ions is achieved by calcium pump, calcium pump is much slower in comparison with a pump of skeletal muscle – longer contraction

Mechanism of contraction

• Beginning of contraction4 Ca2+ bind with regulatory protein calmodulin

Complex Ca-calmodulin activates enzyme myosin kinase (a phosphorylating enzyme)

Light chain of of each myosin head (regulatory chain) become phosphorylated, the head has the capability of binding with the actin filaments

• Cessation of contraction:When the concentration of Ca2+ falls bellow a critical

level, all processes automatically reverse except for the phosphorylation of myosin head

Enzyme myosin phosphatase splits the phosphate from the regulatory light chain

Smooth muscle - contraction

Smooth muscle – membrane potential

Smooth muscle has more voltage-gated calcium channels and very few voltage-gated sodium channels than skeletal m.

Importance of Ca2+ ions in generating smooth muscle action potential – phase plateau of AP, contraction

Slow wave•Resting potential –50 to –60 mV•Spontaneous slow wave (some smooth muscle is self-excitatory)•Slow wave can initiate action potentials (-35 mV)•The more AP, the stronger contraction

Contraction without action potentials

• In multiunite smooth muscle, Ca2+ ions can flow into the cell through the ligand-gated Ca2+ channel – ligand – acetylcholine, norepinephrine

• Action potentials most often do not develop

• Membrane potential do not reach a critical level for generating action potential because the Na+ pump pumps sodium ions out of the cell

Regulation of smooth muscle

Smooth muscle are regulated by autonomic nervesNerve fibers do not make direct contact with smooth muscle fibers – they formed so-called diffuse junctionTerminal axons have multiple varicosities, containing vesiculesIn the multiunite type of smooth cells, the contact junctions are similar to the end plate of skeletal muscle

Striated Smooth

Sarcomere Yes No

Nuclei Many One

Sarcoplasmatic ret. Large Small

T-tubules Yes no (caveoli)

A:M ration 2:1 15:1

Length of Actin Short Long

Actin fixing Z-line Dense bodies

Conduction speed High Low

Contraction speed High Low

Resting potential -90mV -60 mV, fluctuate

Expandibility Small large (10x)

Striated Smooth

Regulatory protein Troponin Calmodulin, myosinkinase

Twitch Fast & short Slow & long

End of contraction ↓ Ca

Spontaneous

↓ Ca

Myosinphosphatase

Consuption of ATP High Low

Connection Synapse Varicosities

Control Motoneurone pacemakersAutonomic NShumorálníMechanical

Fatigue Yes Almost not

striated smooth

Neuromediator Acetylcholine Acetylcholine

(nor)Adrenalin

Source of Ca Sarcoplasm ret Extracellular space