Light-activated ion channels for remote control of neuronal firing.

Abstract

Neurons have ion channels that are directly gated by voltage, ligands and temperature but not by light. Using structure-based design, we have developed a new chemical gate that confers light sensitivity to an ion channel. The gate includes a functional group for selective conjugation to an engineered K(+) channel, a pore blocker and a photoisomerizable azobenzene. Long-wavelength light drives the azobenzene moiety into its extended trans configuration, allowing the blocker to reach the pore. Short-wavelength light generates the shorter cis configuration, retracting the blocker and allowing conduction. Exogenous expression of these channels in rat hippocampal neurons, followed by chemical modification with the photoswitchable gate, enables different wavelengths of light to switch action potential firing on and off. These synthetic photoisomerizable azobenzene-regulated K(+) (SPARK) channels allow rapid, precise and reversible control over neuronal firing, with potential applications for dissecting neural circuits and controlling activity downstream from sites of neural damage or degeneration.

• Authors: Matthew Banghart, Katharine Borges, Ehud Isacoff, Dirk Trauner, Richard H Kramer
• Journal: Nature neuroscience (Nat Neurosci) Vol. 7 Issue 12 Pg. 1381-6 (Dec 2004) ISSN: 1097-6256 [Print] United States
• PMID: 15558062 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Ion Channels

Topics

• Action Potentials (physiology)
• Animals
• Cells, Cultured
• Female
• Hippocampus (physiology)
• Ion Channel Gating (physiology)
• Ion Channels (chemistry, physiology)
• Neurons (physiology)
• Photic Stimulation (methods)
• Rats
• Rats, Sprague-Dawley
• Xenopus laevis