Summary of events during
skeletal muscle contraction
Rest
actin and myosin uncoupled
calcium stored in SR
Excitation
nerve impulse generated
ACH released from the vesicles
sarcolemma depolarized
muscle impulse transmitted through the
fiber
calcium released from the cisternae
calcium binds to troponin
actin binding sites activated
myosin ATPase activated
Contraction
Myosin cross-bridges swivel
Release ADP + Pi
Actin slides over myosin
Regeneration
ATP attaches to myosin
actin and myosin dissociate
ATP → ADP + Pi
contraction process repeats
Relaxation
ACH decomposed by cholinesterase
nerve impulse stops
calcium removed by calcium pump
actin binding sites inhibited
(Tn/tropomyosin complex returns to
original position)
muscle returns to resting state
Excitation Contraction Coupling
process by which myofibrils translate
nerve impulses into muscle contraction
depolarization of t-tubule membrane (a
change in the membrane potential) results
in the calcium release from the terminal
cisternae of the SR
this results in muscle contraction
also know calcium is resequestered in the
SR via active calcium-ATPase pumps
not clear is how the change in membrane
potential of the t-tubule system is
communicated into the SR to cause
calcium release
Structure and Function of the
Triad
t-tubules and SR communicate at the triad
junction
a ryanodine receptor is a large protein
complex which is the release channel of
the sarcoplasmic calcium, located at the ttubule SR junction
the receptor has two parts: channel region
and a large cytoplasmic region
within t-tubule is another protein
complex, believed to be the voltage
sensor which controls the opening and
closing of the ryanodine receptor, this is
the DHP or dihydropyridine receptor
complex
hypothesized: ryanodine receptor and
the DHP receptor interact with each
other to cause the action potential to
induce calcium release from the SR
Theories of Communication
Calcium-induced tubule membranes
Voltage-induced changes in the t-tubule
Changes in the voltage gradient
Calcium induced tubule
membranes
Cause an opening of the calcium channel
calcium released:
stimulation of t-tubule induces a release of
calcium ions from the gates within the SR
Con: block calcium release channels of the
cell membrane does not inhibit calcium
release from the SR
Nor reduce tension development
Also, amount of calcium needed to induce
release is not clear (may not be
physiologic)
Voltage-induced changes in the
t-tubule
induce the formation of D-myosinositol
1,4,5-triphosphate (IP3)
IP3 then increases the permeability of the
SR membranes to cause calcium release
Pros: elevated IP3 production has been
demonstrated in skeletal muscle
following electrical stimulation
Release of calcium in skinned fibers
induced by IP3
An augmented muscle response following
inhibition of IP3 breakdown
A reduction of IP3 release from RBCs
Cons: is the concentration of IP3
necessary for activation and is its rate of
activation physiologic?
Changes in the voltage gradient
Activation of calcium is due to perturbation
of the normal H+ gradient across the SR
membranes
Cons: the pH changes during muscle
contraction may be too small to induce the
necessary gradients in order to stimulate
calcium release
Hypothesized Mechanisms for
ECC
Calcium-induced calcium release
Chemical intermediate
Allosteric Interaction
Calcium induced calcium release
stimulation of t-tubules causes a small
amount of calcium to cross the t-tubule
membrane
an amount insufficient to cause muscle
contraction
This induces the release of additional
calcium in greater amounts, from the SR
(calcium channels are open)
Cons: blocking the DHP channels of the ttubule membrane does not inhibit calcium
release from the SR
Or decrease force development
Are the amounts of calcium required
physiologic?
Chemical Intermediate
voltage-induced changes in the t-tubules
induce the formation of inositol 1,4,5
triphosphate (InsP3)
IP3 then increases the permeability of the
SR membranes to cause calcium release
Pros: after electrical stimulation, there is an
elevated production IP3
The release of calcium in skinned fibers
induced by IP3
If IP3 release from the RBCs is inhibited,
there is a reduction of calcium transients in
skeletal muscle
If IP3 breakdown is inhibited, there is an
augmented skeletal muscle response
Cons: is the concentration of IP3 necessary
for activation?
Is its rate of activation physiologic?
Allosteric Interaction Hypothesis
(aka, Plunger Hypothesis)
there is a mechanical or allosteric link
between DHP channels of the t-tubules
and the ryanodine channels of the SR
(junctional foot proteins)
There is a foot structure composed
primarily of SR calcium channel proteins
clustered next to the t-tubule membrane
called channel protein or electron dense
feet
This suggests a role for protein-protein
interactions to transmit the depolarization
signal across the junction. Most popular
mechanism of signal transmission is a variant of
the plunger hypothesis:
Imagine a mobile positive charge in the ttubule membrane (it may be associated
with the DHP voltage sensor)
The charge is connected by a rod to a plug
in the calcium release channel of the SR
Depolarization of the t-tubule membrane
causes charge movement in the t-tubule
membrane
Results in the unplugging of the SR
calcium release channel
Suspect that the mobile charge is
contained within specific amino acids
contained within a segment of the DHP
receptor complex
Ryanodine receptor complex has a large
cytoplasmic portion spanning the gap
between membranes, and able to contact
the voltage sensors of the DHP complex
Skeletal Muscle Fiber Types
not all skeletal muscle has the same
biochemical or functional characteristics
are generally classified according to their
primary dependence on different metabolic
pathways for the production of ATP.
Nomenclature based on
Myosin ATPase pH lability: histochemical
staining
Glycolytic staining
Oxidative staining
Fiber sub-types:
Type I, SO (slow oxidative), red fibers,
slow
Type IIa FOG (fast oxidative glycolytic),
intermediate fibers
Type IIb FG (fast glycolytic), white, fast
Type IIc rare, undifferentiated fiber,
perhaps found during re-innervation or
motor unit transformation, between I and
IIa on the continuum of metabolic potential
Type IIx, not classified
Slow twitch fibers:
fatigue resistant, good for prolonged
exercise
primarily synthesized ATP via aerobic
energy transfer
recruited for aerobic activities such as
prolonged moderate exercise
have a smaller resting membrane
potential, -50-70mv, versus 80-90mv in
fast muscle
longer latency period due to less
extensive SR
low activity of myosin ATPase
slow speed of contraction
low glycolytic capacity
increased size and number of
mitochondria
higher levels of myoglobin
higher concentrations of mitochondrial
enzymes
increased blood flow -- increased
capillarization
Fast twitch fibers:
activated in short-term, sprint activities,
and forceful contractions which rely
primarily on anaerobic metabolism for
energy
important in stop and go and change of
pace activities
more extensive SR
greater capability for electrochemical AP
transmission (due to increased SR)
high activity level of myosin ATPase
rapid SR calcium release and uptake
high rate of cross-bridge turnover
development
intrinsic speed of contraction and tension
is 2-3 times that of ST fibers
primarily use the glycolytic system for
energy transfer