MUSCLE PHYSIOLOGY
Ass. Prof. Dr. Emre Hamurtekin
EMU Faculty of Pharmacy
SKELETAL MUSCLE
STRUCTURAL PROPERTIES
STRUCTURAL PROPERTIES
STRUCTURAL PROPERTIES
STRUCTURAL PROPERTIES
SARCOTUBULAR SYSTEM
• T system and sarcoplasmic
reticulum
• T system of transverse tubules
is continous with the
sarcolemma
• The SR has enlarged terminal
cisterns at the junctions
between the A and I bands.
• Triad
• T system provides a path for
the rapid transmission of
action potential
• SR is an important store of Ca
SARCOTUBULAR SYSTEM
ELECTRICAL and ION CHARACTERISTICS of
SKELETAL MUSCLE
•
•
•
•
Resting membrane potential: -90 mV
Action potential lasts: 2-4 ms
Conducted along the muscle fiber : 5 m/s
Ion distribution is similar to that across the
nerve cell membrane.
CONTRACTILE RESPONSES
• Muscle twitch: A brief contraction folllowed by relaxation
which is caused by a single action potential.
MOLECULAR BASIS OF CONTRACTION
• In resting muscle:
 Troponin I covers the sites where myosin heads
interact with actin
 Myosin head contains tightly bound ADP
• Step 1: Following an action potential, cytosolic Ca increases and binds to
Troponin C
• Step 2: Weakening of Troponin I interaction with actin and myosin-actin
cross bridges occur.
• Step 3: Upon formation of the cross-bridge, ADP is released.
• Step 4: ADP release causes a conformational change and myosin head
moves the thin filament (power stroke).
• Step 5: ATP binds to the free site on the myosin. This leads to a
detachment of the myosin head from the thin filament.
• Step 6: ATP is hydrolyzed and cycle is completed.
MOLECULAR BASIS OF CONTRACTION
• Excitation-contraction coupling:
The process that a depolarization of a muscle fiber initiates a
contraction
• Ca is reduced in the muscle cell by SERCA and
this causes a cessation of interaction between
actin and myosin
• Pumping of the Ca back into the sarcoplasmic
reticulum causes relaxation
TYPES OF CONTRACTION
ISOMETRIC
ISOTONIC
(same length)
(same tension)
SUMMATION OF CONTRACTIONS
• Contractile mechanism does not have a refractory
period.
• Summation of contraction: Additional contractile
response that is added to the already present
contraction.
• Tetanic contraction (tetanus): Because of the
activation of contractile mechanism occurs repeatedly
before any relaxation occurs, individual responses fuse
into one continuous contraction.
• Tetanic contraction:
– Complete tetanus
– Incomplete tetanus
SUMMATION OF CONTRACTIONS
MOTOR UNIT
• Each single
motor neuron
and the muscle
fibers it
innervates
constitute a
motor unit.
• The number of
muscle fibers
in a motor unit
varies.
CARDIAC MUSCLE
MORPHOLOGY
• The striations are
similar to those
in skeletal
muscle.
• Z-lines are
present.
• There are large
numbers of
mitochondria.
• The muscle fibers
branch and
interdigitate.
• Intercalated disks
Muscle fiber resmi
MORPHOLOGY
• Along the sides
of the muscle
fibers next to the
disks, the cell
membranes form
gap junctions.
• Cardiac muscle
function as if it
was a syncytium:
 Intercalated disk
 Gap junctions
• T-system in
cardiac muscle is
located at Z-lines
(not at the A - I
junction).
ELECTRICAL PROPERTIES
• The resting membrane potential: -80 mV.
• A plateau is present before the membrane
potential returns to the baseline.
• Cardiac myocytes contain at least 2 types of
Ca channels (T- and L-types), but the Ca
current is mostly due to opening of slower Ltype Ca channels.
ELECTRICAL PROPERTIES
Phase 0
Phase 1
Phase 2
Phase 3 to
Phase 4
initial rapid
depolarization
and the
overshoot
the initial rapid
repolarization
prolonged
plateau
final
repolarization to
resting
membrane
potential
opening of
voltage-gated Na
channels.
closure of Na
channels and
opening of one
type of K channel.
slower but
prolonged
opening of
voltage-gated Ca
channels.
closure of Ca
channels and a
slow delayed
increase of K
efflux through
various types of K
channels.
MECHANICAL PROPERTIES &
METABOLISM
• The contractile response of cardiac muscle lasts
about 1.5 times as long as the action potential.
• The cardiac muscle can’t be tetanized!!!
• Abundant blood supply, numerous mitochondria,
high content of myoglobin.
• Normally less than 1% of the total energy is provided
by anaerobic metabolism.
• Under basal conditions caloric needs of the heart are
provided by,
– 35% by carbohydrate
– 5% by ketones and amino acids
– 55% by fat
SMOOTH MUSCLE
MORPHOLOGY
• No visible cross-striations.
• Actin & myosin II are present and slide on
each other to produce contraction .
• Instead of Z-lines, there are dense bodies.
• Contains tropomyosin but troponin is absent.
• Sarcoplasmic reticulum is less extensive.
• Contain few mitochondria.
MORPHOLOGY
TYPES
• A) Unitary (visceral) smooth muscle
B) Multiunit smooth muscle
• Unitary (visceral) smooth muscle
– i.e. intestine, uterus, ureter
– occurs in large sheets
– has many low-resistance gap-junctional connections
(syncytial function)
• Multiunit smooth muscle
– i.e. iris of the eye
– individual units (few or no gap junctional bridges)
– Each multiunit smooth muscle cell has endings of nerve
fibres.
TYPES
ELECTRICAL & MECHANICAL ACTIVITY
• Unitary smooth muscle is characterized by the
instability of its membrane potential.
• Continuous, irregular contractions (tonus)
• Resting potential: from -20 mV to -65 mV.
• Excitation-contraction coupling in unitary
smooth muscle is a very slow process.
• Contractions of multiunit smooth muscle are
more discrete, fine and localized than unitary
smooth muscle contractions.
CONTRACTION & RELAXATION
• Source of Ca increase in unitary smooth muscle:
– influx through voltage or ligand-gated plasma
membrane channels.
– efflux from intracellular stores through the RyR
– efflux from intracellular stores through the IP3
receptor Ca channel.
• The lack of troponin: myosin must be
phosphorylated for activation of myosin ATPase.
– Calmodulin-dependent myosin light chain kinase
CONTRACTION & RELAXATION
CONTRACTION & RELAXATION
CONTRACTION & RELAXATION
Contraction
Dephosphorylation of myosin
by myosin light chain
phosphatase
Relaxation, or sustained
contraction due to the latch
bridge and other mechanisms
CONTRACTION & RELAXATION
• Unitary smooth muscle contracts when
stretched in the absence of any extrinsic
innervations unlike other types of muscle.
• Intestinal smooth muscle preparation:
Norepinephrine (relaxation) X acetylcholine (contraction)
• NO-nitric oxide- (released from endothelial cells) leads
to relaxation of blood vessel smooth cell.
THE END