Cardiomyopathy Flashcards
What is visceral smooth muscle?
Smooth muscle located in the GI tract, bladder, uterus
Number and position of nuclei in
- cardiac muscle
- skeletal muscle
- smooth muscle
Cardiac muscle: 1-4, located centrally
Skeletal muscle: Many nuclei, located on outer edge
Smooth muscle: One nucleus, located centrally
Which types of troponin are present in
- cardiac muscle
- skeletal muscle
- smooth muscle
Cardiac muscle: I, T and C
Skeletal muscle: C
Smooth muscle: None
Where would you find a diad and a triad?
Diad in cardiac muscle: One t-tubule to one SR
Triad in skeletal muscle: One t-tubule to two SRs
Where is the t-tubule located in cardiac muscle?
Z disc
Where is the t-tubule located in skeletal muscle?
A-I junction
What causes smooth muscle contraction?
Calcium forms a complex with calmodulin
Complex activates MLCK
MLCK phosphorylates regulatory light chains
Causes contraction
MLCP removes phosphates from regulatory chains
Causes relaxation
What effect does Gs subunit receptors have on smooth muscle contraction?
Increase in adenylate cyclase Increase in cAMP cAMP inhibits MLCK No phosphorylation of light chains No contraction
What effect does Gi subunit receptors have on smooth muscle contraction?
Decrease in adenylate cyclase Decrease in cAMP No inhibition of MLCK Phosphorylation of light chains Contraction
What effect does Gq subunit receptors have on smooth muscle contraction?
Hydrolyses PIP2 into IP3 and DAG IP3 releases Calcium from SR Calcium binds calmodulin Complex activates MLCK Phosphorylation of light chains Contraction
Also causes activation of Rho-Kinase
Rho-kinase inhibits MLCP
What is the function of DAG?
DAG remains within the membrane
Activates Protein kinase C
How does NO mediate smooth muscle contraction?
NO activates guanyl cyclase Increase in cGMP cGMP activates MLCP Removes phosphates from light chains Relaxation
Which receptors are present on vascular smooth muscle for control of vasoconstriction/contraction?
a1 - contraction
a2 - contraction
AT1 - contraction
V1 - contraction
What G-protein subunit are AT1 and V1 receptors coupled to?
Gq
How is vasodilation initiated?
Parasympathetic NS releases Ach, binds to muscarinic Ach receptors
How does immunohistochemistry work?
Used to detect presence (or lack of presence) of specific proteins in a tissue slice
Antigens are labelled with fluorophores which emit light upon excitation
What can immunohistochemistry be used to diagnose?
Can diagnose ARVC (after death) by staining a myocardial biopsy for desmosomal proteins
What are the steps of immunohistochemistry?
Tissue slice fixed on formalin to expose proteins
Block non-specific binding sites with serum
Wash away anything unbound with saline tween
Incubate with antibodies
Reaction to visualise
What are the advantages of direct immunohistochemistry?
More specific
Fewer steps
Just primary antibodies used
What are the advantages of indirect immunohistochemistry?
More sensitive
Allows for amplification of the protein when it is in low abundance
Involves using secondary antibodies, producing by injecting another species with IgG antibodies
What is the cause of ARVC?
Autosomal dominant mutation
Mutation in desmosomal proteins
Less adherence of cardiomyocytes - separate and die during contraction
Replaced with scar and fat tissue which does not conduct as well
Right ventricle wall thins and ventricle enlarges
What are the phases of a pacemaker action potential (just numbers)?
4, 0, 3, 4
What happens during the ‘4’ phase of a pacemaker action potential?
At -60mV, HCN (slow sodium) channels open
Allows influx of the ‘funny current’ causing depolarisation
Depolarisation causes opening of T-type and L-type calcium channels
What happens during the ‘0’ phase of a pacemaker action potential?
The action potential threshold is at -40mV
T-type calcium channels close but L-type channels remain open allowing rapid depolarisation
