Muscle Flashcards
Skeletal muscle
Voluntary control
Sarcomere arranged end to end to form a myofibril
Multiple peripheral nuclei, striations
Tendons
Numerous large mitochondria for ATP production
SR releases CA2+for contraction
No gap junctions or desmosomes
Smooth muscle
Elongated muscle fibres (cells)
Pointed ends and single large, oval nucleus
Found in hollow organs
No straitions
Dense bodies
Few mitochondria
The sarcomere
Functional unit of skeletal and cardiac muscle
Between z lines
A band only region containing myosin
H zone contains myosin
M line, centre of sarcomere, myosin attachment site; creatinine kinase, myomesin and c-protein
Nebulin
Present in sarcomere in skeletal muscle
Determines exact length of actin filaments
Nebulette
Present in sarcomere in cardiac muscle
Can bind both actin and alpha-actinin so it is believed to be involved in anchoring sarcomeric actin to the Z-disc
Titin (connectin)
Titin is a template protein - it positions myosin between two z-discs
Largest known protein
N-terminal links with z-disc, overlaps with titin from the next sarcomere; capped by protein called T cap
Titin interacts with actin in the Z-disc through 45AA domains called z-repeats which bind with N-terminal of alpha-actinin
Intercalated disc
Contain desmosomes and gap junctions
Strong cell-cell cohesion
low resistance pathways
To allow spread of excitation from one cell to another
Three junction types in the ICD
Fasciae adherens(adherens junctions): transmit mechanical force from cell to cell
Gap junctions: mediate chemical and electrical coupling between myocytes
Desmosomes: form attachment sites for IF
Gap junctions
Water filled channels linking cytoplasm of neighbouring cells
Allow exchange of inorganic ions and other small water solvable molecules CA2+
Connexin
4x hydrophobic transmembrane segments
Connexon
Hemichannel
6x connexins
Multiple connexons => gap junction
Cardiomyocytes express gap junctions composed of…
Cx40
Cx43
Cx45
Gap junctions function:
Transfer of metabolites to cells incapable of their synthesis
Coordination of cellular metabolism and development via intracellular secondary messengers
Phosphorylation of connexin subunits leads to what structural changes of a connexon channel?
Closes it
reversible conformational changes in gap junctions in response to (3)
Cytosolic pH change
Increased in cytoplasmic CA2+
Increases in neurotransmitters
Costameres
Sub-sarcolemmal protein assembles that connect sarcomere to sarcolemma in striated muscle cells
Anchor myofibrils to sarcolemma by Z-lines
Maintain spatial organisation of myofibrils
Also play a role in cellsignalling
Explain the role of costameres in mechanotransduction
Laterally transmit contractile forces from sarcomere across the sarcolemma to ECM and neighbouring muscle cells
Mechanical fortification of sites of lateral force transmission across the sarcolemma to minimise stress on the relatively labile lipid layer
Functions of the Z disc
Continuity between sarcomere
Link actin filaments of one sarcomere to actin filaments in the adjacent sarcomere
Cytoskeleton anchor to actin and titin
Roles in signalling and muscle haemostasis
Act as mechanical stress sensors in cardiomyocytes
Protein network in the Z disc
Desmin (IF) encircles the z-disc and cross-links to plasma membrane desmin -> forms links between neighbouring z discs -> maintains integrity
Complexes in muscle
Dystrophin - glycoprotein complex
Integrin - metavinculin complex
Focal adhesion
(Plectin 1)
Dystrophin-glycoprotein complex
Specialised adhesion complex linking ECM to cytoskeleton
Muscular dystrophy occurs when….
Gene encoding dystrophin is mutated
Duchenne muscular dystrophy key facts
X-chromosome 21;2
X linked recessive
Rapid muscle degeneration => death
Pathogenesis of DMD
Loss of DGC=> increase CA2+ concentration in muscle fibres => increase muscle degeneration and necrosis(due to activation of CA2+ dependent proteases)
Changes in MAPK and GTPase signalling => increase damage and increase CA2+ influx
Cardiac muscle
Heart
Length: 50-100um; width 10-20um
Short branching cylinders; single central nucleus; striations
ICD junctions join cells end-to-end
Intrinsic rhythm; involuntary autonomic modulation
Lifelong rhythm; variable force
M line
Centre of sarcomere
Myosin attachment site
Creatinine kinase, myomesin and c-protein
