Ion channels set the rhythm of life

One of the most fascinating aspects of human physiology is the ability of our hearts to beat autonomously, without any external stimuli. At the core of this process is the heart’s natural pacemaker, the sinoatrial (SA) node, which has the ability to generate electrical impulses autonomously, thanks to the special properties of its pacemaker cells. These cells are adept at spontaneously producing rhythmic impulses (cardiac action potentials), which then travel through the heart’s conduction system, prompting the heart muscle to contract.

But what makes pacemaker cells autonomously generate action potentials? The answer is what scientists have aptly named “funny channels.” These remarkable channels, formally known as hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, play a pivotal role in the regulation of heart rate. They possess a few quite unique characteristics that set them apart from many other channels: they activate upon hyperpolarization, have a mixed permeability for potassium and sodium, and are modulated by cyclic nucleotides. These unusual characteristics made the researchers call these channels “funny.”

Now, how do funny channels help generate action potentials in pacemaker cells? After an action potential, when the membrane potential drops below −40/−50 mV, the funny current gets activated, supplying a depolarizing inward current. This inward current drives the membrane potential toward the threshold at which voltage-gated T-type (CaV3.1) and L-type (CaV1.3) calcium channels are activated, thereby setting the stage for the next action potential.

Given their key role in regulating pacemaker activity in the SA node, funny channels are regarded as a therapeutic target. One drug, Ivabridine, which is a HCN inhibitor, was approved by EMA and FDA and is now in clinical use for heart failure. Ivabradine selectively inhibits the HCN current and reduces cardiac pacemaker activity, decreasing the heart rate.

As we celebrate American Heart Month, it’s essential to recognize the significance of ion channels in heart health. These tiny channels regulate every beat of our hearts and are central to our very existence. They set the rhythm of our lives, from the pulsing moments of excitement to the calm, steady beats of rest. The mighty channels breathe a spark of life into our developing hearts while we are still embryos, and they can stop that ticking clock inside us. To enjoy more moments of joy, more beats of love, and more opportunities to make a meaningful impact, take care of your hearts. Consider how lifestyle choices can impact heart health and support cardiovascular research or engage in heart-healthy activities as a way to give back to this vital organ that keeps us alive.