05.02.3 Ion Channels

An example of an ion channel polymorphism is the HERG channel, a potassium channel on the heart.  On the electrocardiogram (ECG),  the QT interval is a measure of ventricular repolarisation (relaxation of heart prior to new beat) (Figure 5.4)

Figure 5.4 Electrocardiogram (ECG) showing QT interval (Copyright QUT, Sheila Doggrell)

The “Long QT syndrome” is associated prolonged relaxation of the heart, such that the heart may not be fully relaxed and ready to beat again.  This leads to syncope (temporary loss of consciousness and posture) and cardiac arrhythmia/sudden death.  This polymorphism is in a particular cardiac potassium channel: the HERG channel and can lead to sudden death in young people. On the cardiac potential, the “Long QT syndrome” represents prolonged repolarisation (Figure 5.5).  

Figure 5.5 Ventricular action potential and ‘Long QT Syndrome’ (Copyright QUT, Sheila Doggrell)

In addition, several drugs have been shown to prolong the QT interval by blocking the HERG, and this leads to an increased risk of cardiac arrhythmias and sudden death.  Several commonly used drugs have been withdrawn, as they have been shown to prolong the QT interval, e.g. some commonly used antihistamines were withdrawn after they had been on the market for several years.  To make sure this does not happen again, in drug development, it is now mandatory to test whether a new drug is an inhibitor of HERG channels. 

Pharmacology InOneSemester,
Mar 24, 2015, 1:34 AM
Pharmacology InOneSemester,
Mar 24, 2015, 1:36 AM