Funny channels

February 8 is Laugh And Get Rich Day. It sounds intriguing, isn’t it? Laugh and get rich. Ha-ha. While I haven’t found any studies showing that laughter can actually increase income, the idea itself is not devoid of logic. Numerous studies have shown that laughter reduces depression, stress, and burnout. It improves mental health, subjective well-being and overall life satisfaction. Naturally, happy employees are more productive and also more liked by their peers, which can lead to a raise. So, all these factors suggest that laughter could potentially make you money. But it’s just an assumption. What we know for sure is that the opposite is often true. Several studies demonstrated that laughter frequency increases significantly with increase in income, meaning that rich people laugh much more frequently than poor. Does anyone know if there’s a Get Rich First and Then Laugh Day?

So, I looked through Pubmed to find out how ion channels are related to laughter but found nothing except that nitrous oxide (N2O), known as laughing gas, inhibits NMDA receptors and T-type calcium channels (Cav3.2/CACNA1H), and activates TREK1 potassium channels. These effects form the basis of N2O anesthesia/analgesia. Other than that, nothing on ion channels and laughter. Maybe it’s because ion channels aren’t funny? Or are they?

In fact, there is a group of channels whose name resonates with laughter – these are hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, also called “funny channels”. They are widely expressed throughout the heart and the central nervous system. In cardiac cells and neurons, these channels control repetitive activity and excitability.

Let’s take a look at the heart, for example. The rate at which our hearts beat is controlled by specialized cells, called pacemaker cells. These cells can spontaneously generate rhythmic impulses (cardiac action potentials) that propagate through the heart’s conduction system and cause heart muscle to contract. And our funny channels play a key role in generation and modulation of these rhythmic impulses in pacemaker cells. If you inhibit these channels, your heart rate will slow down. And this is exactly how the heart failure drug, Ivabradine, works – it inhibits HCN channels in the heart and slows down the heart rate.

You might ask, why are they called funny? The current produced by funny channels was first identified in Purkinje fibers in 1960s. It was believed to be a potassium current deactivating on hyperpolarization, and so, was called IK2. And despite the fact that there were some inconsistencies in the behavior of IK2, such as the current disappeared in sodium-free solutions… for the next 10 years IK2 was regarded as pure potassium current. And it wasn’t until 1979 that Brown, DiFrancesco, and Noble demonstrated that IK2 is not a pure potassium current, but is rather an inward current activated during hyperpolarizations negative to about -50 mV. It turned out that the channel has a mixed permeability for potassium and sodium.

You know, at the time of its discovery, the fact that the channel had mixed permeability and could be activated by hyperpolarization was kind of unusual. So, scientists apparently had a lot of fun with this channel, characterized its behavior as “funny” and gave it a new name “the funny channel”.