In a recent discovery, scientists have found that a specific type of channel found in the pacemaker cells of the heart could lead to new and better heart drugs. These channels, known as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, are responsible for the electrical impulses that drive the heart.
In the study, the researchers used a new technique to identify the channels in the pacemaker cells. They then used a computer model to study how the channels function.
The results of the study showed that the HCN channels are responsible for the electrical impulses that drive the heart. The channels are also responsible for the heart’s ability to speed up or slow down.
The findings of the study could lead to new drugs that can target the HCN channels. These drugs could be used to treat heart conditions such as arrhythmias.
The study was conducted by researchers from the University of Leicester in the UK. It was published in the journal Nature Communications.
A decade ago, when researchers at Stanford University were looking for new genes that control the electrical signals in the heart, they had no idea that their discoveries would eventually lead to a potential new class of drugs for treating cardiac arrhythmias.
But that’s exactly what has happened, thanks to the serendipitous finding of a never-before-seen gene that encodes a protein called HCN4. This protein forms channels in cell membranes that enable electrical impulses to pass from one cell to the next – a crucial process in the heart’s electrical system.
Last month, the Stanford team – led by cardiologist and geneticist Michael Snyder, PhD – published a study in the journal Nature Medicine detailing how a variant of the HCN4 gene is linked to an increased risk of atrial fibrillation, a type of heart arrhythmia. The study also showed that a drug that targets HCN4 channels can help correct atrial fibrillation in a animal model.
“This is a prime example of how understanding the genetics of a disease can lead to the development of better treatments,” says Snyder, who is the Charles and Diane Duncan Distinguished Professor and chair of the Department of Genetics at Stanford.
The discovery of HCN4 channels – and their role in electrical signaling – dates back to 2006, when Snyder and his colleagues set out to identify new genes involved in electrical signaling in the heart. Using a family of arrhythmia-prone rats, the team identified a previously unknown gene – now known as HCN4 – that was responsible for a defect in electrical signaling.
Further studies revealed that HCN4 codes for a protein that forms channels in cell membranes – known as “pacemaker channels” – that enable electrical impulses to pass from one cell to the next. These channels are found in the cells of the heart’s conduction system, which regulate the heart’s rhythm.
In the new Nature Medicine study, the Snyder team set out to see if variants of the HCN4 gene were linked to atrial fibrillation in humans. The team analyzed the genomes of more than 13,000 people with atrial fibrillation and more than 25,000 people without the condition.
The analysis revealed that a particular variant of the HCN4 gene – known as HCN4-A564T – was linked to an increased risk of atrial fibrillation. This variant is found in about 1 percent of the population, and carriers of the variant have about a 25 percent increased risk of atrial fibrillation.
To understand how this variant affects HCN4 channels, the team turned to animal studies. Using a mouse model of atrial fibrillation, the team showed that the HCN4-A564T variant leads to changes in the structure of HCN4 channels that result in impaired electrical signaling.
The team also showed that a drug that specifically targets HCN4 channels can help correct atrial fibrillation in the mouse model. This finding raises the possibility that drugs targeting HCN4 channels could one day be used to treat atrial fibrillation in humans.
“This is an exciting discovery that could lead to the development of new drugs for treating atrial fibrillation,” Snyder says. “The next step is to develop drugs that specifically target HCN4 channels.”
