OG's email: oamaidoh@mcw.

edu

Skel muscle : Lecture 1

• Structure of striated muscle
1. Organization: fasiculus, Fiber, fibril, filaments
i. 2 types of filament:
1. Thick - myosin
a. 2 heavy chains - form tail and head
b. Head is an ATPase
c. 4 light chains
i. 2 essential
ii. 2 regulatory
2. Thin - actin, troponin, tropomyosin
a. Actin - binds myosin
b. Troponin
i. C subunit - binds ca++ - necessary for contraction
ii. T subunit - binds tropomyosin
iii. I (inhibitory) subunit - blocks active sites of myosin
c. Tropomyosin - blocks actin active sites
Goal - thin to slide over thick
Pulls towards actin center of myosin
I band shortens with each contraction, with max contraction I band disappears
End result - generate contractile force
Sarcomere
I band - thin only
A band - where myosin is
Mech of contractile force generation
Point is to convert chemical energy to mechanical
Chemical - ATP on myosin head
How: via filament sliding
Mechanism
ATP binds myosin head - causes it myosin to release actin
ATPase on head hydrolyzes ATP - called relaxed state (cocked state)
Released energy from this hydrolysis allows myosin to pull down actin filament
Note: in death when there is no ATP generation, myosin can't relax - get rigor mortis
Cross bridge forms at actin active site
Power stroke - phosphate is released
this released energy allows myosin head to pull actin towards center - SLIDING
ADP released - just myosin bound to actin
Cycling REPEATS: ATP comes along and releases myosin
Thus dissociation of cross bridge needs ATP
Cross bridge cycling
Ca++ binds troponin C
Stimulates troponin T to bind tropomyosin
Leads to tropomyosin to change configuration
Active sites of actin are exposed
Cause troponin I and tropomyosin undergo conformational change
Actin binds myosin
Mech of excitation-contraction coupling
DHP receptor
Ryonine receptor
Process
AP travels down sarcolemma
AP is propagated into T tubule
AP activates foot proteins
DHP is a voltage sensitive Ca++ channel - it is opened by depol (by AP)
Change in DHP configuration pulls Ryanodine receptor on SR
Ca++ can exit Ry receptor of SR
Ca++ inflx into cyto
Ca"++ binds troponin C
Cross bridge
2 sources of Ca++ EC coupling
Extracellular - when DHP opens due to Ap
Intracellular - from SR due to RyR

Skel muslce : Lecture 2

Regulate control of muscle contraction
AP in nerve
AP reaches pre-synaptic cleft of nerve terminal
AP opens voltage gated Ca++ channels, allows Ca++ to enter neuron and it induces ACh vesicle to fuse
with plasma mem
ACh is released into synaptic cleft
Botulinum toxin blocks release of ACh from muscle - no muscle contraction - no wrinkles
ACh will bind receptor on muscle - ACh receptor is a nicotinic Na+ channel (in skel muscle - it is
musacrinic in smooth)
Na++ influx - depol occurs
Voltage-gated Na channels open (due to depol) - fast
Further influx and greater depol
Voltage - gated K+ channels open - hyperpol - slow
SINCE, Na+ channels are faster get net depol
End-plate potential (Em of cell) reaches threshold - leads to generation of AP
AP is propagated down muscle
This is necessary for EC coupling - which is necessary for contraction
Na+ channels close - stops further depol
K+ channels remain open longer - leading to hyperpolarization

characteristics whole muscle contraction

Summation - leads to inc in force
Inc # of motor unit
Inc stimulation of single muscle fiber
Tetanus - due to max summation
Smooth contractile force is generated
Constant contraction of fiber
Fatigue - depletion of glycogen stores
Diff types of muscle fibers
Fast - glycogen - fatigue more
Slow - oxidative

Skel muscle: Lecture 3

Isotonic vs isometric
Isotonic - constant force, velocity of shortening changes
Vmax is reached when load is 0
Is constant in skel muscle
In smooth muscle can inc Vmax by inc Phosphorylation of myosin
In cardiac - Inc by inc contractibility
Load - velocity curve - see drawings

Isometric - constant length - tension that develops in muscle varies

T max at mid length moderate overlap btw actin and myosin
Length tension curve - see drawing
Mechanical props of skel muscle - see graphs

Smooth muscle
Structure
Ratio is 15:1 (in skel is 2:1) allows for more shortening
Thick - myosin
Thin - actin, tropomyosin (no troponin)
Dense bodies - site of attachment for thin filaments
Alpha actin
Veniculin
Intermediate - link dense bodies
Desmin
Vimentin
Gap junctions - excitation spreads
Contractile Force generation
Contraction is due to [ca]i. regulated by myosin (in skel was reg by actin)
Process
In in [ca]i activates MLCK
Ca++ binds calmodulin
Ca++- calmodulin activates MLCK
MLCK activates myosin via phosphorylation of myosin light chain via ATP hydrolysis - allows cycling to
begin
Myosin changes conformation binds actin forming cross bridge - ADP + Pi are released (1 Pi still bound)
Myosin head hydrolyzes ATP - power stroke = contraction
Cross bridge cycling (1 ATP/cycle) continues until [Ca{i falls
Dec ca -> inactivation of MLCK
Myosin phosphotase (activated by ca++ dec) removes from myosin light chain
Inc ins ATPase activity, inc in cycling - continued cycling
Contraction is ATP dependent (vs skel muscle where relaxation is ATP dependent)

Smooth vs skel
Smooth
dec in contraction time/onset due to slower atpase activity (cross bridge cycling)
Get a wider L- tension curve
Slower contraction is good - allows for more stretch (ie bladder)
Dec in Vmax - slope of load -velocity curve is less steep
To inc Vmax - inc number of myosin heads phosphorylated (can't inc Vmax in skel)
Inc in force of contraction/cross-sectional area of fiber
Ex - uterine contraction in child birth
Inc in degree of shortening
Ie - uterus
Due to slower cycling and more cross bridge formation
Inc in force maintenance
Dec in energy expenditure
Dec SR density - more dependent extracellular ca++

Cardiac muscle - KNOW WIGGER'S DIAGRAM

Wigger's diagram
7 phases
A - atriole systole - get inc in left atrial pressure, and thus inc venus pulse
B - isovolumic ventricular contraction - AV valve closes causing 1st heart sound
C - rapid ejection phase - aortic valve opens
D - reduced ejection
(NOTE: in our wigger's C&D are put together into a single phase called "ejection")
E - isovolumic relaxation - aortic valve closes when its pressure is lower than in ventricle, get 2nd heart
sound
F - rapid ventricular filling - 3rd heart sound - can hear in normal children, but is bad in adults
Easiest way to orient yourself is to start with ECG and work your way up
Heart sounds occur when valves close