Download Smooth muscle

MUSCLE (skeletal, cardiac & smooth)
Systems Biology: Tissue & organ Function Block
Lecture 13
10/28/09 1:30-3:00pm
Ruben Mestril, Ph.D: rmestri@lumc.edu 327-2395
Reading Assignment: L.S. Costanzo, Physiology 3E., Chap. 1, p. 32-41: Chap 4, p. 137-139.
LEARNING OBJECTIVES
1.
To describe the 3 types of muscle and give examples of their function.
2.
To describe thick and thin muscle filaments.
3.
To contrast the arrangement of thick and thin filaments in smooth and striated muscles.
4.
To describe differences between single-unit and multi-unit smooth muscles.
5.
To compare how calcium triggers activation of the contractile apparatus in smooth and striated muscles.
REVIEW QUESTIONS
1.
What are the similarities and the differences of the molecular events that initiate contraction in smooth and
skeletal muscle.
2.
Describe the interaction between actin and myosin.
3.
Describe the sources of energy for muscle contraction and explain how energy is transferred to the
contractile mechanism.
Three types of Muscle: Skeletal, Cardiac and Smooth muscle.
Function is to generate force or movement in response to a physiological stimulus.
• Skeletal muscle: maintains contractile force for long periods.
• Cardiac muscle: contracts for brief periods with each heartbeat, but for a lifetime.
• Smooth muscle: must contract without fatigue for very long periods.
Muscle Contraction: In all three muscle types contraction depends on rise in free Ca2+ concentration.
Each muscle type has specialized plasma membrane, cytoskeleton, endoplasmic reticulum and metabolic
pathways for energy generation and utilization.
MUSCLE FILAMENTS
Thin filaments (actin, tropomyosin and troponin). Actin made up of filamentous or Factin is closely associated to the actin binding proteins: tropomyosin and troponin.
Thick filaments made up of multiple myosin-II molecules (hexamer: 2 heavy chains,
2 regulatory light chains and 2 alkali light chains). Heavy chains bind the actin of the thin
filaments, alkali light chains stabilize myosin head regions and the regulatory light chain regulates
the ATPase activity of myosin.
Figure 1-21 Structure of thick (A) and thin (B) filaments of skeletal muscle. Troponin is a complex of three proteins: I,
troponin I; T, troponin T; and C, troponin C.
Muscle Contraction.
Striated muscle cells are densely packed with myofibrils that contain ordered arrays of
thick and thin filaments.
Striated muscle (skeletal and cardiac muscle) where each myocyte or fiber contains
myofibrils in the diameter of a Z-disk. Each myofibril is made up of sarcomeres composed of
myofilaments, both thick filaments made up of myosin and thin filaments made up of actin.
The A-bands mark the center of the sarcomere (containing the thick filaments) and are the
area of cross-bridge formation between thin and thick filaments. The I-bands are outside of the A-band
and contain the thin filaments.
Figure 1-22 Arrangement of thick and thin filaments of skeletal muscle in sarcomeres.
TRANSVERSE (T) TUBULES
Transverse tubules are extensive network of muscle cell membrane or sarcolemmal membrane that are
responsible for carrying depolarization from the action potentials at the muscle cell surface to the
interior of the muscle fiber.
The T tubules are in close contact with the sarcoplasmic reticulum that is the site of storage and release
of Ca2+ during excitation-contraction coupling.
Figure 1-23 Transverse tubules and sarcoplasmic reticulum of skeletal muscle. The transverse tubules are continuous with
the sarcolemmal membrane and invaginate deep into the muscle fiber, making contact with terminal cisternae of the
sarcoplasmic reticulum.
Muscle cell excitation.
Skeletal muscle contracts in response to neuromuscular synaptic transmission where one neuron
innervates several skeletal muscle cells to form a “motor unit”. Transmission is through inotropic
(nicotine) Ach receptors.
Cardiac muscle contracts in response to the propagation of electrical signals from one cardiac cell to
another across gap junctions. Electrical signals are generated in the pacemaker region of the heart
(sinoatrial node), that generates action potentials transmitted from cell to cell through gap junctions.
Chemical synapses only modulate but do not initiate cardiac contraction.
In smooth muscle, neuromuscular transmission may initiate contraction or may just modulate
contraction initiated by another mechanism.
Figure 1-24 Temporal sequence of events in excitation-contraction coupling in skeletal muscle. The muscle action potential
precedes a rise in intracellular [Ca2+], which precedes contraction.
Excitation – Contraction Coupling
•Invaginations of the sarcolemma facilitate communication between the surface of the cell and it’s
interior.
•In skeletal muscle, depolarization of the T-tubule membrane leads to Ca2+ release from the
sarcoplasmic reticulum at the Triad.
•In cardiac muscle, Ca2+ entry through L-type Ca2+ channels is amplified by Ca2+-induced Ca2+
release from the sarcoplasmic reticulum.
•In smooth muscle, both extracellular and intracellular Ca2+ activate contraction.
•Smooth muscle contraction may also occur independently of increases in [Ca2+]i.
Terminating Contraction
•In skeletal, cardiac and smooth muscle, terminating contraction requires re-uptake of Ca2+ into the
sarcoplasmic reticulum.
•In smooth muscle, terminating contraction also requires dephosphorylation of the myosin light chain.
Figure 1-25 Cross-bridge cycle in skeletal muscle. Mechanism by which myosin "walks" toward the plus end of the actin
filament. A-E, See the discussion in the text. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; Pi, inorganic
phosphate.
Regulating Muscle Contraction
•Muscle contractions produce force and/or shortening and, in the extreme, can be studied under either
isometric or isotonic conditions.
•Muscle length influences tension development by determining the degree of overlap between actin and
myosin filaments.
•At high loads, the velocity of shortening is lower because more cross-bridges are simultaneously active.
•In a single skeletal muscle fiber, the force developed may be increased by summing multiple twitches in
time.
•In a whole skeletal muscle, the force developed may be increased by summing the contraction of multiple
fibers.
•In cardiac muscle, increasing the entry of Ca2+ enhances the contractile force.
•In smooth muscle, contractile force is enhanced by increasing the entry of Ca2+, as well as by increasing
the Ca2+ sensitivity of the contractile apparatus.
•Smooth muscle maintains high force at low energy consumption.
Figure 1-26 Length-tension relationship in skeletal muscle. Maximal active tension occurs at muscle lengths where there is
maximal overlap of thick and thin filaments.
Figure 1-27 Initial velocity of shortening as a function of afterload in skeletal muscle.
EXCITATION-CONTRACTION COUPLING IN CARDIAC MUSCLE CELLS
•Cardiac action potential is initiated in the myocardial cell membrane resulting in an inward Ca 2+
current.
•Entry of Ca2+ into the myocardial cell produces an increase in intracellular Ca2+ concentration that
triggers release of more Ca2+ from stores in the SR (Ca2+ -induced Ca2+ release).
•Ca2+ binds to troponin C so tropomyosin is moved out of the way and actin and myosin are able to
interact. Actin and Moysin cross-bridges form and break permitting the thin and thick filaments
move past each other producing tension.
•The magnitude of the tension developed by myocardial cells is proportional to the intracellular
Ca2+ concentration.
Figure 4-18 Excitation-contraction coupling in myocardial cells. See the text for an explanation of the circled numbers. SR,
Sarcoplasmic reticulum.
In cardiac muscle, Ca2+ entry through L-type Ca2+ channels is amplified by Ca2+ -induced Ca2+
release from the sarcolasmic reticulum
Donald Bers, Nature 415:198-205; 2002.
Smooth muscle may contract in response to either neuromuscular synaptic transmission or
electrical coupling.
• Smooth muscle may be formed into “multiunit smooth muscle” where smooth muscle cells are
innervated by more than one neuron and there is little electrical coupling (gap junctions) between
smooth muscle cells. Found mostly in the iris and ciliary body of the eye, the piloerector muscles
of the skin and some blood vessels.
• Other smooth muscles depend mainly on electrical coupling through gap junctions permitting
coordinated contraction among cells to form the “unitary smooth muscle” found in the
gastrointestinal tract, the uterus and many blood vessels (also called visceral smooth muscle).
Figure 1-28 Sequence of molecular events in contraction of smooth muscle. When myosin and actin bind, cross-bridges form
and produce tension. When nonphosphorylated myosin and actin bind, latch-bridges form but do not cycle; a tonic level of
tension then is produced. ADP, Adenosine diphosphate; ATP, adenosine triphosphate; Myosin-P, phosphorylated myosin; Pi,
inorganic phosphate.
Action potentials of smooth muscle may be brief or prolonged.
In unitary smooth muscle, action potentials maybe a simple spike, a spike followed by a plateau or a
series of spikes on top of slow waves. Some of these smooth muscle cells can initiate spontaneous
electrical activity. Some of this spontaneous electrical activity results in regular and repetitive oscillations
referred as slow waves.
In multiunit smooth muscle, action potentials usually do not occur.
Figure 1-29 Mechanisms for increasing intracellular [Ca2+] in smooth muscle. ATP, Adenosine triphosphate; G, GTPbinding protein (G protein); IP3, inositol 1,4,5-triphosphate; PIP2, phosphatidylinositol 4,5-diphosphate; PLC, phospholipase
C; R, receptor for hormone or neurotransmitter.
COMPARISONS BETWEEN MUSCLE TYPES
Muscle type
Skeletal
Cardiac
Smooth
Mechanism of excitation
Neuromuscular transmission
Pacemaker potentials,
electrotonic depolarization via
gap junctions
Synaptic transmission,
Hormone-activated receptors,
Electrical coupling,
Pacemaker potentials
Ca2+ sensor
Troponin
Troponin
Calmodulin
Excitation-contraction
coupling
L-type Ca2+ in T-tubule
coupling to Ca2+ release
channel (ryanodine receptor in
SR
Ca2+ entry via L-type Ca2+
channel triggers Ca2+ -induced
Ca2+ release from SR
Ca2+ entry via voltage-gated
Ca2+ channels; Ca2+ and IP3mediated Ca2+ release from
SR; Ca2+ entry through storeoperated Ca2+ channels
Terminates contraction
Breakdown of Ach by
acetylcholinesterase
Action potential repolarization
Myosin light chain
phosphatase
Metabolism
Oxidative, glycolytic
Oxidative
Oxidative