Download Muscle relaxants

Muscles
Striated
Cardiac
Smooth
Excitability and contractibility
animations
• http://www.dnatube.com/video/4875/Physiology-of-musclecontraction-and-relaxation
• http://www.dnatube.com/video/1306/Role-of-myosincrossbridge-in-the-contraction-of-muscle
• http://www.dnatube.com/video/1952/Sliding-filament-causescontraction-of-muscle
• http://www.dnatube.com/video/4154/Cellular-mechanism-ofmuscular-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++ pump
Physiological depletion of sources of ATP
(reversible) – contracture, spasm, cramp
Irreversible 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 contraction
4 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
Slow wave
•Resting potential –50
to –60 mV
•Spontaneous slow
wave (some smooth
muscle is selfexcitatory)
•Slow wave can
initiate action
potentials (-35 mV)
•The more AP, the
stronger contraction
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
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 nerves
Nerve fibers do not make direct contact with smooth muscle
fibers – they formed so-called diffuse junction
Terminal axons have multiple varicosities, containing vesicules
In the multiunite type of smooth cells, the contact junctions
are similar to the end plate of skeletal muscle
Sarcomere
Nuclei
Sarcoplasmatic ret.
T-tubules
A:M ration
Length of Actin
Actin fixing
Conduction speed
Contraction speed
Resting potential
Striated
Yes
Many
Large
Yes
2:1
Short
Z-line
High
High
-90mV
Expandibility
Small
Smooth
No
One
Small
no (caveoli)
15:1
Long
Dense bodies
Low
Low
-60 mV,
fluctuate
large (10x)
Regulatory protein
Twitch
End of contraction
Consuption of ATP
Connection
Control
Fatigue
Striated
Troponin
Smooth
Calmodulin,
myosinkinase
Fast & short Slow & long
↓ Ca
↓ Ca
Spontaneous Myosinphosphatase
High
Low
Synapse
Varicosities
Motoneurone pacemakers
Autonomic NS
humorální
Mechanical
Yes
Almost not
Neuromediator
Source of Ca
striated
smooth
Acetylcholine Acetylcholine
(nor)Adrenalin
Sarcoplasm ret Extracellular space