Throughout your life, your heart will clock up around three billion beats, all thanks to the heart’s own pacemaker cells, which sit in the sinoatrial node (SAN). But as we age, dysfunction can creep in, resulting in events such as cardiac arrhythmias. We’ve typically relied on rabbits and mice to model and understand this link between aging and cardiac dysfunction, yet these animals have significantly shorter lifespans, fewer lifetime heartbeats, and are relatively distant from us genetically. So are these rodents relevant models?
Well, a team of scientists have turned their attention to a new potential model: Microcebus murinus, the gray mouse lemur (GML). The GML is one of the smallest primates, lives for up to 12 years in captivity, and, much like us, generates around three billion heartbeats. The researchers’ work might just provide a glimpse into why primates live so long with such a high cardiac workload, while also offering insights into heart rhythm impairment.
Targeting the right cells
In the initial characterization steps of this new GML model, the team wanted to look at isolated heart cells, specifically pacemaker myocytes. The SAN is one of the common victims of age-related dysfunction, which can lead to periods of very slow heart rates (HRs) known as bradyarrhythmias. In severe cases, patients may need artificial pacemakers.
To ensure that they were looking at the right cells, the researchers used Alomone’s highly specific anti-HCN4 antibody as a functional SAN marker. This marker was chosen because the specialized pacemaker cells in the SAN express the hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), which enables the pacemaker current, known as the funny current (If).
Expression of HCN4 confirmed that they had successfully isolated SAN cells and allowed them to continue with the electrical characterization of these pacemaker cells (Figure 1).
HCN4 expression in GML SAN tissue and isolated myocytes
Insights from a lemur heart
Through careful study, the team found that GMLs demonstrate a refined autonomic modulation of cardiac activity, with HRs ranging from 120 to 555 beats per minute, and that the SAN activity is regulated by cholinergic and adrenergic agonists.
The study explored how GMLs, humans, and other primates generate a significantly higher lifelong number of heartbeats compared to other mammals. This cardiac endurance may contribute to the exceptional longevity of primates, which is why the team proposes further genomic analysis to investigate the genetic basis of primate longevity.
Just how similar are GMLs to humans? Well, the presence of specific ion channels in GML hearts suggests significant similarities to the pacemaker mechanisms we see in humans. The researchers also note differences in ventricular repolarization and left atrium enlargement between GMLs and mice – another potentially shared characteristic with larger mammals and humans. In aged GMLs, the basal HR slowed, similar to the reduction we see in aged humans. Overall, the data here support the use of GMLs as a model to study the dysfunction we often observe in our aging hearts.
It is therefore clear that cardiac pacemaker activity in GMLs and other primates can provide us with insights into the mechanisms underlying our exceptional longevity, and perhaps even help scientists develop clinical applications for cardiovascular diseases.
The heart of your research
If you’re interested in cardiac research, we have several reagents you might be find useful:
- Anti-HCN4 Antibody (#APC-052)
- HCN4 Blocking Peptide (#BLP-PC052)
- Guinea pig Anti-HCN4 Antibody (#APC-052-GP) is raised in guinea pig and can be used in multiplex staining studies in conjunction with any of our antibodies raised in rabbit. This antibody has been raised against the same epitope as #APC-052.
- Anti-HCN1 Antibody (#APC-056)
- Anti-HCN2 Antibody (#APC-030)
- Anti-HCN3 Antibody (#APC-057)
- HCN Antibody Explorer Kit (#AK-205) – the Explorer Kit contains HCN antibodies with their respective peptide control antigen. An ideal tool for screening purposes.
- Cardiac Channel Blocker Explorer Kit (#EK-345)
- Cardiac CaV Channel Antibody Explorer Kit (#AK-310)
- Cardiac KCNK (K2P) Channel Antibody Explorer Kit (#AK-340)
- Cardiac Kir Channel Antibody Explorer Kit (#AK-330)
- Cardiac KV Channel Antibody Explorer Kit (#AK-320)
- Pacemaker Cell Marker Antibody Kit (#AK-620)