Matthew R Banghart | PubMed Health

PubMed2006

Engineering light-gated ion channels.

Ion channels are gated by a variety of stimuli, including ligands, voltage, membrane tension, temperature, and even light. Natural gates can be altered and augmented using synthetic chemistry and molecular biology to develop channels with completely new functional properties. Light-sensitive channels are particularly attractive because optical manipulation offers a high degree of spatial and temporal control. Over the last few decades, several channels have been successfully rendered responsive to light, including the nicotinic acetylcholine receptor, gramicidin A, a voltage-gated potassium channel, an ionotropic glutamate receptor, alpha-hemolysin, and a mechanosensitive channel. Very recently, naturally occurring light-gated cation channels have been discovered. This review covers the molecular principles that guide the engineering of light-gated ion channels for applications in biology and medicine.

Animals↗

PubMed2006

Light-induced depolarization of neurons using a modified Shaker K(+) channel and a molecular photoswitch.

To trigger action potentials in neurons, most investigators use electrical or chemical stimulation. Here we describe an optical stimulation method based on semi-synthetic light-activated ion channels. These SPARK (synthetic photoisomerizable azobenzene-regulated K(+)) channels consist of a synthetic azobenzene-containing photoswitch and a genetically modified Shaker K(+) channel protein. SPARK channels with a wild-type selectivity filter elicit hyperpolarization and suppress action potential firing when activated by 390 nm light. A mutation in the pore converts the K(+)-selective Shaker channel into a nonselective cation channel. Activation of this modified channel with the same wavelength of light elicits depolarization of the membrane potential. Expression of these depolarizing SPARK channels in neurons allows light to rapidly and reversibly trigger action potential firing. Hence, hyper- and depolarizing SPARK channels provide a means for eliciting opposite effects on neurons in response to the same light stimulus.

Action Potentials↗