Light-gated ion channels

As ion channels influence many aspects of biology, artificially light-responsive ion channels can facilitate experimental manipulation, allowing neuroscientists to better understand brain function. Because neurons use ion channels to transmit sensory information, light-gated ion channels could restore the senses of those such as the blind who have neural damage.

Dirk Trauner and colleagues at the University of California, Berkeley, reviewed engineered light-gated ion channels in the Dec. 26 issue of Biochemistry. They noted that photoswitchable chemicals such as azobenzenes and spiropyrans have been exploited to render ion channels sensitive to light. Ion channels that have been made light sensitive to study their properties include the nicotinic acetylcholine receptor (nAChR), gramicidin A, a voltage-gated potassium channel and — most recently — α-hemolysin. Making nAChR light sensitive allowed the researchers to study channel kinetics without considering molecules that stimulate them, a previously insurmountable limitation. Using modified potassium channels — dubbed SPARK (synthetic photoisomerizable azobenzene-regulated K+) — they have studied action potential firing of hippocampal neurons.

Light-gated ion channels could deliver drugs to target tissues, and light could trigger the channels to expand, allowing for controlled drug release. Toward such a system, Ben L. Feringa and Wim Meijberg introduced a cysteine into a channel that is known to open upon mechanical stimulation. They alkylated the cysteine with a caged carboxylic acid, and irradiation with 366-nm light uncaged the compound, causing the channel to expand. This system could carry small-molecule sensors as well as drugs.

Two naturally occurring light-gated ion channels, called channelrhodopsins, have already been exploited to study action potentials in nervous systems. The reviewers noted that channelrhodopsins could have much more potential for neurobiological applications. For instance, altering the rate of firing of action potentials or their selectivity for calcium and potassium could yield interesting outcomes.

The reviewers concluded that light-gated ion channels can potentially reveal mechanisms of neural signaling and function, restore the senses of patients with neural damage and serve as drug-delivery vehicles. (Biochemistry, December 2006, pp. 15129-15141.)