Wednesday, 21 November 2012

Electricity is even more important in biology than previously thought

Mary Shelley,s gothic masterpiece on the shores of Lake Geneva nearly two centuries ago, she brought Frankenstein’s fictional monster to life using the power of electricity; a form of energy that scientists had recently discovered, which seemed to play a key role in the functioning of the body.
Today, biologists are realising that electricity is even more important than was hitherto thought – so much so that some are talking about a new bioelectrical revolution. It not only governs the contraction of our muscles and carries impulses through our nerves, but also holds the key to a host of illnesses, from the most intense migraines to cystic fibrosis.

A lecture in the Royal Institution, London, the Oxford University physiologist Frances Ashcroft explained how this revolution in bioelectricity has happened.

While the electricity we use to power motors, make lights shine and bring our computers to life relies on electrons – the fundamental sub-atomic particles which carry electrical charge – the electricity in our bodies is carried by larger, more complex charged atoms, or ions, which are found in salts such as sodium chloride. While electricity in wires travels at the speed of light, (around 186,000 miles per second), electrical signals are carried around our bodies at a far slower (if still rapid) half a mile per second, or about 1800 mph.

As bioelectricity flashes in and out of our cells, it generates currents of a few picoamperes – about a hundred billionth of the current that makes a light bulb glow. Somehow, the ions carrying these currents have to find a way past the insulating greasy membrane that protects the watery contents of every cell.

The realisation that cell membranes are studded with tiny pores (constructed from specific proteins), which allow the free movement of ions, dates back to in the 1950s and the pioneering studies of Alan Hodgkin and Andrew Huxley in Cambridge and Bernard Katz at University College London.
These pores are ion channels, and they regulate all life, from the moment of conception until we draw our last breath. Indeed, according to Ashcroft, these channels are truly the “spark of life” – the title of her recent book on the subject.

From the lashing of the sperm’s tail to the beating of our hearts, the craving for yet another chocolate, or the feel of the sun on your skin, everything is underpinned by ion channel activity.
In 1984, Ashcroft discovered an ion channel through which potassium ions leave cells and observed that it was closed by the breakdown of glucose, triggering the release of insulin. She was so excited that she did not sleep; the next morning, thought she had made a mistake.

She hadn’t. Two decades later it was found that a rare childhood form of diabetes resulted from a defect in this channel and, in a remarkable twist, could be treated by taking pills called sulphonylureas, initially trialled as a treatment for typhoid.

It turns out that faulty ion channels are actually responsible for a remarkably wide range of human and animal diseases. Pigs that shiver themselves to death, myotonic goats that stiffen so much they topple over when startled, humans with cystic fibrosis, epilepsy, heart arrhythmias or migraine – all are victims of ion channel dysfunction.

Mutations in sodium channels, for example, underlie inherited forms of epilepsy (when an electrical storm erupts in the brain), migraine headaches, heart rhythm disturbances, paralysis, and some chronic pain syndromes. In the past few years, important clues to understanding what goes wrong, and how this can be fixed, have come from working out what ion channels look like.
Sodium channels – which allow sodium ions to pass – are found in “excitable” cells such as the neurons in your brain, or the cells found in heart muscle, or the nerve cells that carry signals of pain, hot or cold.

Their atomic structure was only solved last year, by William Catterall’s team from the University of Washington in Seattle. Many drugs work by interacting with ion channels and knowing the shape of the protein, and what the drug-binding sites look like, is expected to stimulate the design of new chemicals, which can alter the protein’s structure.

Poisons target ion channels, too. In the past few days, Sylvie Diochot and Anne Baron from the French National Centre for Scientific Research (CNRS) have reported a remarkable discovery. The venom of the black mamba, one of the world’s nastiest snakes, contains chemicals that block nerve ion channels.

These chemicals, mambalgins, stop a specific type of ion channel found in pain cells from opening. By doing so, they relieve pain as effectively as morphine, without its side effects. Thanks to the second electrical revolution, expect a new generation of drugs to fine-tune the electrical workings of your heart, nerves and brain.

Roger Highfield is Director of External Affairs at the Science Museum

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