Most Common: Duchenne MD

Pathology - characterized my gradual muscle destruction, DEATH BY HEART OR RESPIRATORY FAILURE

Ultimate Cause - Sex linked gene, 1/3500 boys

Mechanistic Cause - Usually, gene makes protein called dystrophin that regulates Ca+ leaks into muscle cells

With disease, no dystrophin, Ca+ leaks are constant which causes proteases to activate and destroy muscle protein

Treatment - cell transplant, gene therapy

Hypothesis 1: cold or overexercise causes afferent AP from muscle to spinal cord, causing muscle reflex contraction. The contraction further stimulates afferent APs to spinal cord --> positive feedback loop

Hypothesis 2: Overexercise w/o fluid & electrolyte replacement --> ion imbalances between ECF and ICF, changes resting membrane potential, results in effects of overstimulation as if lots of APs firing

Binding of ATP causes myosin to release actin

After death, membranes in muscle begin to decompose

Ca+ floods muscle cells

Muscles contract

No ATP to bind to myosin head to cause muscles to relax

Eventually muscle protein decomposes, relaxes

[image]

Spindle Shaped, single nucleus

typically arranged in sheets

contraction moves contents forward (blood vessels, GI tract)

[image]

Subcellular Structure of Smooth Muscle:

Three Types of Smooth Muscle Filaments

Thick Myosin Filament

Thin Filaments (actin, tropomyosin, NO TROPONIN, instead dense bodies<same protein as Z lines>)

Intermediate Filament (support cell shape)

Smooth muscle has

NO T-TUBULES 

&

UNDERDEVELOPED SARCOPLASMIC RETICULUM

True or False?

There are NO Z LINES in smooth muscle

but dense bodies, made of same protein as Z lines

dense bodies are anchored to cell membrane, and actin filaments are anchored to dense bodies

SMOOTH MUSCLE CONTRACTION STEPS IMG

[image]

1. Ca+ channels on smooth muscle membrane open, Ca+ from ECF diffuses into ICF down concentration gradient

2. Ca+ activates enzyme called CALMODULIN

3. Activated CALMODULIN in turn actives enzyme MYOSIN LIGHT CHAIN KINASE (MLCK)

4. Actived MLCK phophorylates MYOSIN by splittin ATP into ADP + Pi

5. Myosin binds with actin, cross bridge cycling begins

6. Ca+ actively out of smooth muscle cell, calmodulin & MLCK return to inactive, enzyme called PHOSPHATASE removes phosphate from myosin

Smooth muscle cells organized into different functional units;

each unit separately stimulated by nerves of autonomic NS (neurogenic)

each unit functions independently

rare: found in

walls of large blood vessels

large airway to lungs

eye muscles

base of hair follicles

[image]

Muscle fibers make up single unit & contract together

Fibers linked by gap junctions, AP travels thru gap junctions, -->contract together

ex. uterus

MYOGENIC (muscle produced)

Autonomic NS

Pacemaker activity - (lymph vessels) in pacemaker cell, membrane depolarizes on its own b/c of automatic changes in channel permeability; once AP fired, spread to rest of smooth muscle via gapjunctions

Slow Wave Potential - (intestines) gradual alternating hyper/depolarizing

swings in potential caused by cyclical changes in rate at which Na+ is transported across membrane

Threshold not always reached, but when it does, burst of APs follow

Modification of contraction Strength in

SINGLE UNIT SMOOTH MUSCLE

fiber tension modified by varying CYTOSOLIC CA+ CONCENTRATION

as cytosolic ca+ concentration increases, so does number of cross bridges cycling

low levels usually maintained, low level contraction always occuring : muscle tone

Modification of contraction strength in

MULTIUNIT SMOOTH MUSCLE

functional unit recruitment

varying cytosolic ca+ concentration

What factors modify Cytosolic Ca+?

(and hence contraction strength for both single & multi unit smooth muscle)

parasympathetic & sympathetic nervous system

hormones

metabolites

mechanical stretch

drugs

Yes, urinary bladder (have to contract full bladder to empty it)

& can even relax when stretched

Slow rate of ATP use

Cross bridges latch onto thin filaments longer

specialized to maintain tension for long periods w/o fatigue

& can accommodate variation in contents volume w/ little change in muscle tension

Striated

contains TROPONIN & TROPOMYOSIN

clear cut LENGTH-TENSION relationship

LOTS OF MITOCHONDRIA

Cells connected by GAP JUNCTIONS

Innervated my AUTONOMIC NS

Fibers joined by branching network