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ad io
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CONTRACCIN
log
Sociedad Per ua
a M
MUSCULAR
olecular
Prof: Pedro Nez
Lima 2013
CONTRACCIN MUSCULAR visin general
Anatoma
Msculo esqueltico
Msculo estriado
Myofiber anatomy
Sarcoplasmic reticulum
lies next to T tubules.
Transverse tubules=
infoldings of sarcolemma.
Myofiber anatomy
Motor Unit
Muscles
Spindle apparatus
Sarcoplasmic Reticulum (SR)
SR - an elaborate, smooth ER that surrounds each
myofibril. Perpendicular (transverse) channels at the
A band - I band junction are the Terminal Cisternae.
SR regulates intracellular Ca2+
Terminal Cisterna
T Tubules (transverse)
T tubules at each A band - I band junction are
continuous with the sarcolemma. The lumen of the
tubule is continuous with the extracellular space.
Conduct electrical impulses to the muscle (every
sarcomere) - signals for
the release of Ca2+ from
adjacent terminal cisternae
T tubule
Triad 2 terminal cisternea and 1 T tubule
Relationship of SR and T
tubules to myofibrils
Msculo esqueltico
SARCOMERE
S1
Light chains
Myosin 160 nm
ELC
Heavy chains
-helical coiled-coil RLC
Z Z
Titin is located in the space between the two filaments, attached at various points to the
myosin, and it runs all the way to the Z-disc at either end of the sarcomere. The protein is
thought to act as a sort of spring mechanism that keeps the myosin filament centered in the
sheath as the whole structure expands and contracts.
Msculo esqueltico
Sliding Filament Theory of
Contraction
Msculo esqueltico ( protenas: miosina 460,000. actina 43,000 TM: 70, T: 18)
Myosin II
heavy
chain
motor
-helical domains
coiled coil light
chains
Myosin II was first studied for its role in muscle contraction, but it functions
also in non-muscle cells.
Myosin II includes 2 heavy chains.
The globular motor domain of each heavy chain catalyzes ATP
hydrolysis, and interacts with actin.
Each heavy chain continues into a tail domain in which heptad repeat
sequences promote dimerization by interacting to form a rod-like -
helical coiled coil.
La miosina pertenece a una superfamilia de protenas formado por 20
tipos
18.4 A rise in cytosolic Ca2+ triggers
muscle contraction
Figure 18-31
18.4 Tropomyosin and troponin regulate
contraction in skeletal muscle
Tropomyosin
Figure 18-32
Tropomyosin consists of two -helical chains (each 35kD) that form a coiled-coil about 40 nm
long which snakes down the middle of the actin helices. It is polymerized end to end along each
of the two grooves of the F-actin filament providing structural stability and modulating the
filament function. Troponin is composed of three subunits which interact strongly with one
another: the Ca2+-binding troponin C (TnC), the inhibitory troponin I (TnI) and the Tm-binding
troponin T (TnT) subunits. The TnT-Tm interaction, which is specific to striated muscles, is
essential for Tn binding to the thin filament with proper stoichiometry of 1 Tn : 1 Tm : 7 actin.
Excitation-Contraction Coupling
Some of the Ca2+ binds to troponin, troponin changes
shape and causes tropomysin to move which exposes
the active binding sites on actin
Myosin heads can now alternately attach and detach,
pulling the actin filaments toward the center of the
sarcomere (ATP hydrolysis is necessary)
Excitation-Contraction Coupling
The short calcium influx ends (30 ms after the action potential ends) and Ca2+
levels fall. An ATP-dependent Ca2+ pump is continually moving Ca2+ back
into the SR.
Tropomyosin blackage of the actin binding sites is reestablished as Ca2+ levels
drop. Cross bridge activity ends and relaxation occurs
Thin Filament Regulatory Proteins
Two Tropomyosin strands spiral around the actin filament and block the
active sites in a relaxed muscle fiber
1. A M + ATP
2. A+ MATP
3. A M ADP Pi
Pi release rate:
Pi
10-20s-1
4. A M ADP +Pi
ADP
5. A M +ADP
Anatoma de la fibra muscular esqueltica y cardica
Fibra muscular esqueltica y cardiaca
Miocito
Fibra muscular cardiaca
Contraccin muscular cardiaca
Contraccin muscular esqueltica
TITIN (TTN). Viene de la mitologa griega del gigante titan, - Es una protena
sarcomrica mas grande, el corazn expresa dos isoformas de TTN, (N2B y
N2BA), que incorpora 4 regiones distintas: Linea Z, banda I, banda A y lnea
M; juega un rol central en la estructura, mecnica y regulatorio del sarcmero
del msculo estriado. El gen del TTN tiene 364 exones y localizado en el gen
2q31, con 4200 kDa, formado de 38.000 residuos de AA, mantiene la
arquitectura y organizacin durante las contraccin y desarrolla tensin pasiva
durante la relajacin
La banda I es responsable de la rigidez del msculo cardiaco y por lo tanto de
la cardiomiopatas en particular la cardiomiopata dilatada(DCM),
caracterizado por disfuncin sistlica con dilatacin del VI o biventricular y
causar la cardiomiopata arritmigena del VD(ARVC), mientras las
cardiomiopatas restrictivas e hipertrficas tiene fondo gentico.
Other Thick Filament Proteins:
Myosin binding protein C MW 140 kDa
binds to myosin tail region
X- protein- MW 134 kDa
H- protein- MW 55 kDa
M-line proteins: creatine kinase (40kDa), M-protein (165 kDa),
myomesin (185 kDa).
M-line
Thin Filament Proteins:
Z-line
F-actin
Z-line
Myosin binding protein C (MyBP-C): Es una protena, filamento delgado, unido
ajustadamente a la meromiosina ligera,(LMM) miosina S2, su finalidad es para
limitar la propiedad contrctil de los miofilamentos,
Regulation
Regulation
Mecanismo de la contraccin ( actina y miosina para formar actomiosina)
Myosin cycle
F-actin is composed of a double
helical strand of thousands of
polymerized G actin (43kd)
molecules.
480 kd subunits
480 kd subunits
2
3
Relacin tensin longitud en la contraccin muscular
Mecanismo de la contraccin y relajacin cardiaca
Myosin RLC
Myosin Phosphorylated-RLC
Acoplamiento farmaco-mecnico: Ang II, catecolaminas, TxA2, contraccin lenta
actuando sobre receptor acoplado de protena Gq>> PLC hidroliza IP2 >>IP3.>>Ca
Acoplamiento electromecnico: PA>> contraccin.
In smooth muscle Ca++ binds to camodulin.
1. MLCK phosphorylates myosin light chains.
2. X-bridge cycling repeats as long as myosin light chains
are phosphorylated
3. A phosphatase finally removes the phosphate to relax
the muscle.
Contraccin de la fibra muscular lisa vascular por estmulo
farmacomecnico.
Relajacin de la fibra muscular lisa vascular
Contraccin de la fibra muscular lisa
Clula muscular lisa presenta contraccin rpida (fsica) lenta (tnica). El
PTR es de -50 -70 mV, y el PA se atribuye al Ca++. La actividad elctrica
puede ser: a.-espontnea, de ondas lentas sin respuesta contrctil y el PA
alcanza -35 produce contraccin fsica. b.- por PA (espigas) y .- PA de
repolarizacin retrasada. (tero).
Msculo liso en comparacin de otros msculos. El ANS no hace contacto
con la fml, si no que se ramifica difusamente entre ellas, secreta el NT. El ANS
no genera, si no modula la contraccin. As en el aparato digestivo la Ach
despolariza y aumenta la actividad migena espontnea y la NA lo contrario,
igual en los bronquios donde el 2 es relajador, en los vasos es al contrario.
En el tero los estrgenos despolariza y la progesterona hiperpolariza.