Hypertrophic Cardiomyopathy Flashcards
T wave
Ventricular repolarisation
What is needed for pacemaker cells to become activated
hyperpolarised
-ve voltage needed at end of phase 3
What are the 5 steps in traditional cloning
- vector preparation
- insert preparation
- ligation
- transformation
- colony screening
What is the difference generally between smooth and cardiac muscle contractions
VSM undergoes slow, sustained, tonic contractions, whereas cardiac muscle contractions are rapid and of short duration.
Give an example of a technology used for recombinant DNA
CRISPR
How common is HCM
1 in 500
What type of mutation are the HCM mutations normally
usually point or missense, bur can be indels
What is the function of myosin ATPase
enzyme that hydrolyses ATP required for actin and myosin cross-bridge formation
What type of genetic dominance/recessiveness is HCM
autosomal dominance
Describe sarcomeres
repeating units making up myofilaments
region between two Z-lines
composed of thick and thin filaments- actin and myosin
What is the effective refractory period (ERP)
stimulation of cell cannot initiate action potential
fast Na channels close and stay inactivated after phase 1
Intercalated discs contain three different types of cell-cell junction. What are these?
- Fascia adherens junctions
- Expanded desmosomes
- Gap Junctions
What is a conjugated protein
a protein bound to something else.
What is faulty in ARVC
Desmosomes
What does the calcium-calmodulin complex activate
myosin light chain kinase
bundles of what make up cardiac myocytes
myofibrils
What is an ECG
A trace showing the rhythm of the heartbeat, where abnormalities can be detected.
What do indels cause in a genetic sequence
frame shift
QT interval
Time taken for ventricular depolarisation and repolarisation
What is HCM
overgrowth of the septum of the heart into the left ventricle, causing outflow tract obstruction so blood cannot flow out of the aortic valve.
P wave
Atrial depolarisation
What gene is most commonly affected in HCM
42% cardiac MyBP-C
What are the ‘funny’ channels gated by
Hyperpolarisation activated cyclic nucleotide gated channels
What is the function of the Hyperpolarisation activated cyclic nucleotide gated channels
They keep generating Aps.
On an ECG trace, how would you work out HR using squares
HR= 1500/number of small squares in RR interval
Or
HR= 300/number of large squares in RR interval
True or false: HCM is frequently asymptomatic until sudden cardiac death
True
Why is depolarisation slower in pacemaker cells
no fast Na+ channels
depolarisation current carried by slow Ca2+ influx
What is ARVC
This is an enlargement of the right ventricle, loss of myocytes, and a fibrotic, fatty heart
When does VSM relaxation occur
when there is reduced phosphorylation of MLC
What is CRISPR cas-9
a CRISPR-associated protein containing two nuclease domains, programmed by small RNAs to cleave DNA
How is the resting membrane potential maintained
K+ channels open - K+ leaves cell making it more -ve
Na+ and Ca2+ channels closed, cannot enter cell
-90mV
Explain the steps of a non-pacemaker cardiac action potential
- Rapid depolarisation due to opening of fast Na+ channels (0)
- Initial repolarisation caused by opening of K+ channel (1)
- Inward Ca2+ movement through L-type channels (slow) which open when membrane reaches -40mV. Plateau phase due to delayed repolarisation. (2)
- Repolarisation occurs when K+ channels open, and closure of Ca2+ channels (3)
- True resting membrane potential (stable). Closed Na+ and Ca2+ channels, open K+ channels. (4)
What are gap junctions
o Provide direct contact between the cardiac cells
o Facilitate electrical communication, so that waves of depolarisation spread rapidly over the entire heart, by passing from cell to cell
o connexin subunits make pores
Q wave
Left to right interventricular septum depolarisation
What are fascia adherens junctions
o Actin filaments attach to thin filaments in the muscle sarcomeres to the sarcolemma
o So, they all contract together in a functional syncytium
What does MLC phosphorylation lead too
cross-bridge formation between the myosin heads and the actin filaments, and smooth muscle contraction.
What are the symptoms of ARVC
palpitations, lightheadedness, and fainting. ARVC can also cause shortness of breath and abnormal swelling in the legs or abdomen.
What can reduce phosphorylation of MLC
- reduced release of calcium by the SR or reduced calcium entry into the cell
- inhibition of MLCK by increased intracellular concentration of cAMP
- phosphatase-activated MLC dephosphorylation.
What is faulty in HCM
sarcomere
What is the purpose of the effective refractory period
protects the heart by preventing multiple APs
at a high HR, the rate would be unable to properly fill and ventricular ejection would reduce
What is the purpose of the intercalated discs of the heart
connect cardiomyocytes to work as a single functional organ/syncytium
What is the name for the invagination of the sarcolemma
Transverse (t) tubule
An increase in which ion stimulates VSM contraction
calcium
Compare the role of Calcium in depolarization of neural/skeletal APs to cardiac APs
neural/skeletal: - caused by opening of Na+ channels
non-pacemaker cardiac: - caused by opening of Na channels, Ca influx prolongs duration of AP causing plateau phase
pacemaker cardiac: - Ca2+ involved in initial depolarisation
Explain the steps of a pacemaker cardiac action potential
- Spontaneous depolarisation (pacemaker potential) caused by funny currents. T-type Ca2+ open; further depolarisation. L-type Ca2+ opens. K+ channels close (4)
- Depolarisation of the AP, caused by increased Ca2+ conductance through L-Type channels. T-type channels close. (0)
- Repolarisation of the AP as K+ channels open and Ca2+ close. Hyperpolarisation reached. Na+ ion channels open, initiating phase 4- also called funny currents or If. (3)
what happens to ‘funny’ and T-type Ca2+ channels near the end of phase 4 (initial depolarisation of pacemaker)
funny currents decline - Na channels close
Ca2+ currents through T-type channels decline - channels close
S wave
Interval between ventricular depolarisation and repolarisation
What is the length-dependent activation of the sarcomere
stretching the sarcomere increases the affinity of Troponin-C for Ca2+
In VSM what does free calcium bind to initatially
Calmodulin
How to calculate penetrance
number of individuals displaying symptoms, divided by the number of individuals with a disease causing mutation x 100
Define penetrance
probability that a person carrying a disease-associated genotype will develop the disease within a given time period
What happens when calcium binds to troponin C
conformational change in troponin complex
myosin head exposed
ST segment
Interval between ventricular depolarisation and repolarisation
What causes phase 0 depolarisation of pacemaker cells
mainly by increased conductance of Ca2+ through L-type Ca2+ channels that open near the end of phase 4
Define recombinant DNA technology
the joining of DNA from two different species, that are inserted into host organisms to produce new genetic combinations
What is unusual about the cardiac pacemaker AP
There is no resting phase or RMP & Ca2+ (instead of Na+) is responsible for main depolarisation.
What are the two types of cardiac action potential
non-pacemaker A.P. - fast response
pacemaker A.P. - slow response
Describe smooth muscle
non-striated, single celled (mononuclear) and is found in organs such as the bladder, GI tract and blood vessels.
What are expanded desmosomes
o strong adhesion between cells
o link to the intermediate filament of the cytoskeleton
o structural integrity
R wave
Early ventricular depolarisation
What 3 proteins make up the thin filament
actin
tropomyosin
troponin
