The ocean of ion channels
To celebrate Christmas this year, we decided to gift everyone in the world by donating to The Ocean Cleanup. You know how we all love the ocean for its beaches, fresh and salty air, and waves lapping rhythmically against the shore. Rarely, though, do we think that those waves are not just carrying seashells but also groundbreaking scientific discoveries.
Some 60 years ago, on the coastlines of Woods Hole, USA, and Plymouth, UK, at the Marine Biological Laboratories, Kenneth Cole and Howard Curtis (Woods Hole) and Alan Hodgkin and Andrew Huxley (Plymouth) laid the foundation for much of our current understanding of neurophysiology and the functioning of nerve cells. The location of both laboratories, just next to the ocean, was crucial, as it provided scientists with direct access to arguably one of the most iconic animal species for ion channel researchers – the squid.
Perhaps it’s fair to say that few other animal species have contributed more to the early development of the ion channel field than the squid. The unusually large size of the squid giant axon, compared to axons found in other animals, made it an ideal model system to study mechanisms of the action potential at that time. The groundbreaking works on squid axons have led to the development of voltage and current clamp techniques as well as to the discoveries concerning ionic mechanisms underlying the initiation and propagation of action potentials. These discoveries were so huge that they earned a Nobel Prize in 1963!
Along with squids, other marine mollusks like cone snails have greatly contributed to ion channel field development. These highly venomous sea snails contain various toxins targeting specific ion channels, making them invaluable for studying ion channel function. Some cone snail toxins have even led to the development of therapeutics now used in clinics. For example, ziconotide (a Cav2.2 inhibitor), a synthetic version of an ω-conotoxin peptide from cone snails, is used for pain treatment, whereas XEP-018, a Nav1.4 blocker inspired by mu-conotoxin from cone snails, is used in cosmetics.
Speaking of toxins, you’ve probably heard of fugu fish, which is considered a great delicacy. Unless carefully prepared, fugu can be very poisonous because of tetrodotoxin (TTX) contained in the liver and some other parts of the fish. TTX, a potent blocker of voltage-gated sodium channels in our nerves and skeletal muscles, is extremely toxic, even more so than cyanide. It blocks signal transmission, inducing paralysis and respiratory failure. Despite strict regulations around selling and serving fugu, the slight risk of consuming deadly fish continues to attract thrill-seekers. But how is it possible that the fugu is not paralyzed by the TTX in its body? In fact, fugu is resistant to TTX due to two mechanisms: a mutation in its Nav1.4 sodium channel, making it insensitive to TTX, and various TTX-binding proteins that prevent TTX from blocking ion channels.
Many ocean inhabitants exhibit fascinating skills controlled by ion channels. For instance, jellyfish and sea anemones use a specialized Cav2.1 voltage-gated calcium channel orthologue in their stinging cells to determine when to sting.
Sharks, rays, and skates have specialized electrosensory organs that detect minute changes in environmental electric fields, aiding in hunting. This ability is mediated by specific low-threshold CaV1.3 channels coupled with BK channels, enabling the detection of weak electrical signals.
Octopuses and squids have a unique sensory ability to taste objects with their tentacles simply by touching them, a phenomenon known as chemotactile sensation. This ability is mediated by chemotactile receptors in the sensory epithelium of arm suckers, which octopuses use to probe surfaces. These chemotactile receptors, having diverged from nicotinic acetylcholine receptors, mediate contact-dependent chemosensation of insoluble molecules.
In conclusion, the ocean is more than just a scenic wonder; it’s a hub of scientific breakthroughs, particularly in ion channel research. Its unique creatures, like squids and cone snails, have been key to major advances in understanding ion channel function and developing new medicines. Supporting efforts like The Ocean Cleanup helps protect this precious resource, ensuring we continue to learn from its hidden depths in the future.