The mechanism behind how the rhythm of the heartbeat is controlled and why many common drugs can cause a potentially fatal abnormal heart rhythm is being deciphered by Oz scientists.
It is estimated around 40-50 percent of all drugs in development will block one of the main 'channels' that carries electricity in the heart and, as a result, can cause heart rhythm problems called cardiac arrhythmias.
The researchers have discovered a key clue as to why this happens, by understanding how the 'gates,' which effectively 'open' and 'close' the channel, operate.
"Just like a set of metal wires that carry electricity to light up our streets, our body has a series of channels that carry tiny charged particles called ions, into and out of cells, to trigger a heartbeat," said Jamie Vandenberg, Head of the Cardiac Electrophysiology Laboratory at the Victor Chang Institute.
"Depending on the position of these gates, many common drugs bind, or attach themselves to these channels, blocking the ions from passing through. This causes what we call Long QT syndrome, where the length of the heart beat is longer than usual, which greatly increases the risk of arrhythmia," said Vandenberg.
The team of researchers, led by Vandenberg, studied the hERG potassium channel, an ion channel that determines how long each heart beat lasts and the channel which is most susceptible to being 'blocked' by drugs.The hERG channel is a particularly 'sticky' channel, in that most drugs will bind to it when the outer gate is closed. What we've done is to discover how these outer gates operate, in the hope that we can then design drugs more effectively to minimise the unwanted side effects.
"The gates to this channel operate in a much more complex way than was previously thought - much like a Japanese puzzle box, they require a series of complicated, interrelated movements to open them. It is not simply a matter of lifting and shutting a lid as was commonly believed," said Vandenberg.
The findings were reported in the journal Nature Structural and Molecular Biology.