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Photochromic Blockers of Voltage-Gated Potassium Channels

Authors


  • This work was supported by a Laboratory Directed Research Development Award from the Lawrence Berkeley National Laboratory (R.H.K.), NSF-DFG grant CHE0724214 (D.T.), the National Institutes of Health Nanomedicine Development Center for the Optical Control of Biological Function (5PN2EY018241; R.H.K. and D.T.), and by a grant from the Human Frontier Science Program (RGP23-2005; R.H.K. and D.T.). We thank F. Tombola and E. Isacoff for insightful discussions, the Isacoff and Yellen laboratories for Shaker clones, and T. Fehrentz for additional experiments (not included).

Abstract

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Light work: Studies into the mechanism of AAQ, a photoswitchable blocker of voltage-gated K+ channels, led to the discovery and development of photochromic ligands that act at the internal tetraethylammonium binding site (see picture). These molecules can be applied from the extracellular side to impart long-lasting photosensitivity on K+ channels in living cells and thereby afford photocontrol of action potential firing in neurons.

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