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Tracking the science of bioelectricityUpdated
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State of the field

Ion Channels & Excitability

The molecular machinery of bioelectricity, and the tools that let researchers watch and control it.

Maturity
Established

Overview reviewed

Where things stand

This is the foundation the rest of the field builds on. The ionic basis of the action potential was described quantitatively by Hodgkin and Huxley in 1952. The patch-clamp technique (Neher and Sakmann, 1976) made it possible to record currents through single channels. Cryo-electron microscopy has since produced high-resolution structures of many voltage-gated and ligand-gated channels.

Active frontiers

  • Seeing voltage. Genetically encoded voltage indicators and voltage-sensitive dyes now let researchers image membrane potential optically, increasingly at single-spike resolution in living animals.
  • Controlling voltage. Optogenetics, which uses light-gated channels and pumps such as channelrhodopsin (introduced to neurons in 2005), lets researchers depolarize or silence chosen cells with light. The same tools are used in developmental and non-neural bioelectricity research.
  • Channelopathies. Inherited channel mutations underlie forms of epilepsy, cardiac arrhythmia, periodic paralysis and pain disorders, and they are a growing target for gene-specific therapies.

What is contested

Less is settled about the roles of classic "neural" channels in non-excitable tissue, where effects are subtler and harder to separate from other functions of the same proteins.

What to watch

Brighter, faster voltage indicators, channel-subtype-selective drugs designed from structures, and therapies for single-gene channelopathies.

Milestones

  1. 1791Galvani's "animal electricity". Luigi Galvani publishes his experiments showing that frog leg muscles contract when touched with metals, arguing that living tissue carries its own electricity. The resulting debate with Alessandro Volta also led to the electric battery.
  2. 1843The nerve impulse is electrical. Emil du Bois-Reymond records the "negative variation", the electrical signal that travels along nerve and muscle and is now called the action potential. He also measures currents leaking from injured tissue.
  3. 1902The membrane hypothesis. Julius Bernstein proposes that a cell's resting voltage comes from a membrane that is selectively permeable to potassium, and that excitation is a temporary breakdown of that selectivity.
  4. 1952Hodgkin–Huxley model of the action potential. Working on the squid giant axon, Alan Hodgkin and Andrew Huxley describe quantitatively how sodium and potassium currents produce the nerve impulse. The model is still the basis of computational neuroscience.
  5. 1976The patch clamp. Erwin Neher and Bert Sakmann record currents through single ion channels for the first time. The technique won the 1991 Nobel Prize and became the standard tool of electrophysiology.
  6. 2005Optogenetics in neurons. Neurons expressing the algal light-gated channel channelrhodopsin-2 are shown to fire on command with millisecond flashes of light, giving researchers precise control over cell voltage.
  7. 2015Bacteria signal with ion waves. Bacterial biofilms are shown to coordinate metabolism with waves of potassium ions released through ion channels, a form of electrical signalling similar to that in neurons.

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