For each of the following 3 conditions associated with arrhy

For each of the following 3 conditions associated with arrhythmias, explain (reason the mechanism of arrhythmia you would expect (e.g. reentry, early afterdepolarization, etc) and the cellular cause (e.g. prolonged APD, slow conduction velocity, etc) given each pathophysiology shown (3 for each). Base your answer on information provided in class and the slides. The answer for the first is provided you do the rest. Keep in mind that some causes may seem paradoxical. For example, a longer than normal APD and shorter than normal APD can cause an arrhythmia, but the mechanisms would be different.

Solution

Ans.) Long QT syndrome (LQTS) is a rare congenital and genetic or non inheritable cardiovascular disease in which heart have repolarization which follow the heartbeat and increase the chance of TdP (TdP is a form of irregular heartbeat that originates from the ventricles).

LQT 1 & LQT 2 Syndrome - In LQT1 condition, mutation is found in alpha unit that slow delayed rectifier potassium channel whereas in LQT2 alpha subunit showed rapid delayed rectifier potassium channel. In LQT1, the current passes through the heteromeric channel (KvLQT1 + minK) is called as IKs. These mutations often cause LQT by reducing the quantity of repolarizing current, which is needed to terminate the action potential, leading to a rise within the impulse duration. These mutations tend to be the most common yet least severe.

LQT3 Synsdrome - In LQT3 condition, mutation is found in alpha subunit of the sodium channel (SCN5A). The current through this channel is termed  as I_Na. The cellular cause of this is often prolonged APD. Depolarizing current through the channel late in the impulse is assumed to prolong APD. The late current is due to the failure of the channel to stay inactivated. As a consequence, it can enter a exploding mode, during that vital current enters suddenly once it ought to not. These mutations are mostly fatal however less common.

Catecholaminergic polymorphic ventricular arrhythmia – Catecholaminergic polymorphic ventricular arrhythmia (CPVT) is caused due to mutations in either one among a minimum of 5 genes, four of which presently studied. Mutations in two genes cause CPVT familial by autosomal dominant (AD) inheritance pattern whereas the different ones follow autosomal recessive (AR) inheritance. In the given question, the explanation for mutation must be defect in calcium induced-calcium release from the sarcoplasmic reticulum (SR).