Muscles Alive!
Excitation – Contraction Coupling,
Mechanics and Adaptations
Anatomy and Physiology
Spring 2016
Stan Misler
<latrotox@gmail.com>
A. Short Review of Skeletal muscle
Machina carnis (machine made of flesh): Tissue using chemical energy
stored in high energy phosphate bonds (hydrolysis of ATP) to generate
cycles of internal tension -> moving of joint across arc or fixing joint
against a load. Muscle force transmitted to tendon
Muscle = parallel bundles of multinucleated cells. Unit of function =
sarcomere of interdigitating actin and myosin filaments
B. Linkage of action potential in muscle plasma
membrane (sarcolemma) to subsequent muscle
contraction (i.e., excitation-contraction or EC coupling)
(i)
Muscle membrane is depolarized by
acetylcholine released from nerve
terminal ->
(ii) Muscle action potential propagates
along T –tubules which have
membrane proteins that can link up
with Ca channels in terminal cisterns
of sarcoplasmic reticulum (SR)
(iii) Pulling out foot process of SR Ca
channel-> release of Ca from SR into
cytoplasm near sarcomeres->
(iv) Ca binding to actin allows interaction
of actin & myosin (cross bridge formation) ->
(vi) Generation of tension: head of myosin
molecule rotates and pulls actin until myosin
head falls off actin.
myosin
Actin
Heads of myosin contacting actin
and forming cross-bridges
C. Details of EC coupling in skeletal myocytes
1. Skeletal myocytes, like nerve cell bodies and axons, conduct action potentials
2. In skeletal myocytes regions of indented plasma membrane, the T tubules, conduct the AP
towards center of fiber where they make close contacts with Ca loaded sarcoplasmic
reticulum (SR, elaborated endoplasmic reticulum)
3. Skinned muscle fibers (plasma membrane stripped off) dipped in fluids of different Ca
concentrations causes fiber contraction with threshold cytosolic [Ca] at least 100 nM as
measured by Ca sensing dye previously injected into the cytoplasm
4. In intact muscle fibers the rise in cytosolic Ca comes from T tubule –SR “electrical synapse” :
Propagation of AP down T-tubule possessing dihydropyridine receptor proteins (DHPR)
changes DHPR configuration allowing it to pull on “foot” of Ca release channel, the
ryanodine receptor, RyR, in terminal cisternae of SR-> localized increase in cytosolic [Ca]
5. Binding of Ca to troponin changes conformation of blocking tropomyosin ->
interaction of head of myosin interdigitating with actin -> actin myosin bond at 45o
from myosin stalk -> actin/myosin cross bridge formation.
D. Actin /myosin crossbridges and contraction.
From interference and electron microscopies, interdigitating actin and myosin filaments are
clearly seen where myosin projections (heads) are uniformly distributed over myosin
filaments except at middle region. With contraction sarcomeres are reduced in length, while
with stretching sarcomeres increase in length. However the lengths of interdigitating actin
and myosin filaments do not change (see left) suggesting that actin and myosin slide past
each other. Also, during contraction heads of myosin are seen to attach to actin and then tilt
pulling actin towards the center of the sarcomere (see right). Since length of putative crossbridge is small (0.2 um) compared with sarcomere contractions of 1 um, during contraction
there must be repeated cycles of attachment/pull racheting pull/detachment
Direction of
sliding of
actin with
respect to
myosin heads
1. Sliding filament model/ swinging crossbridge model for
contraction = myosin heads cyclically walking along actin
(left) myosin head attaching to actin, twisting/ tilting -> pulling actin and then
falling off at extreme position after binding ATP. New cross bridges can be
formed as long as ATP be hydrolyzed and there is sufficient local cytosolic Ca
vs. (right) poorly breakable actin/myosin bonds at low cytosolic [ATP] = rigor
complex and rigor mortis until proteins breakdown
Tilting / twisting and
dragging
to dissociate
2. Length-tension and force-velocity curves basic to muscle
contraction are best explained by sliding filament hypothesis
a. Length-tension curve: Optimization of pre-contraction sarcomere length to
one which provides optimal actin/myosin filament overlap and presumed
cross-bridging opportunity (2.1 um), gives largest tension with in response to
repeated or tetanic muscle stimulation (= jittery tension at almost no change in
sarcomere length).
b. Generating a force - velocity curve
The lower the load the
sarcomere must
support, (i) the smaller
the average number of
cross-bridges needed
to form to support the
load, (ii) the faster the
muscle shortens , (iii)
the faster the
dissociation of actin –
myosin complex (less
resistance to head
tilting
3.
4. Adapting muscle to specific task.
Increasing # sarcomeres in series (longer fiber) ->
greater speed and extent of maximum contraction
while increasing # of sarcomeres in parallel (thicker
fiber) -> greater maximum force of contraction
E. Types of muscles: how they look and function
Skeletal Muscle
1.
2.
3.
Tension generates movement of part of body in relation to external
environment (force on tendon and movement of joint). This is critical for
coarse movements (walking) or fine movements needed for communication
(speech, writing and pointing)
Individual non-communicating muscle fibers are grouped into motor units
innervated by a single motor neuron originating in the spinal cord.
The depolarizing end-plate potential sets off an muscle action potential of
several ms duration that propagates along the muscle surface as well deep
into the fiber via T-tubules. This triggers the releases Ca from internal stores
in SR. Muscle twitches of ~ 50 ms in duration are set off
Operational view of motor unit:
motor nerve fired continuously by an electrode placed in
single spinal motor neuron (MN) results in glycogen loss by
hundreds of muscle fibers the MN innervates
Cardiac muscle
1. Atria and ventricles are cardiac chambers composed of networks of non-innervated,
striated muscle cells conducting long duration APs and connected to one another by
electrical junctions through which K ions flow.
2. The cardiac impulse begins with spontaneously firing of APs by sinoatrial node located at
junction between vena cava and right atrium spread by specialized conducting fibers to
atria and ventricles.
3. Action potentials, first propagating in atria and later in ventricles, are 200-300 ms in
duration with 150 ms plateaus near 0 mV, the latter due to slow opening and slow
inactivation of voltage dependent Ca channels. Each AP sets off contractile tension
lasting nearly 300 ms which empties by ~80% the contents of both atria and ventricles.
Cardiac myocyte EC coupling: Ca entry
induced Ca release from SR (CICR)
Long plateau of cardiac AP provides long opening of plasma membrane
Ca channels and thus longer “trigger Ca” entry to release SR Ca
Positive inotropic effect in cardiac muscle:
while its shortening velocity is smaller than that of
skeletal both maximal velocity and force can be
increased by catecholamines
1.
Smooth
muscle
Hollow organs in digestive, respiratory and reproductive tracts are enclosed by non-
striated, spindle-shaped smooth muscle fibers which move fluids by changing the
diameters of the tubes. These fibers have dense bodies at the surface into which thin
actin filaments insert and more interiorly in the cell interact with small bundles of thick
myosin filaments.
2. The smooth muscle impulse begins with spontaneously firing of APs in by a subset of noncontractile pacemaker fibers and spread via electrical junctions to contractile fibers.
3. Action potentials are 50 -100 ms in duration and set off contractions as long as 1 s in
duration.
4. synapses made by nerve viscosities largely onto pacemaker fibers, change the efficiency of
pacemaker impulses while synapses formed by nerve varicosites on contracting muscle
cells change the force of contraction
Smooth muscle E-C coupling
pathways for entry of Ca and
release of Ca from SR
Unique way that Ca
allows x-bridge formation
Velocity of shortening of smooth muscle is much smaller
than skeletal muscle but energy efficiency is much greater:
smooth muscle can maintain tonic tension with little consumption of
ATP due to slow detachment of x-bridges