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The light-gated cation channel channelrhodopsin-2 (ChR2) has rapidly become an important tool in neuroscience, and its use is being considered in therapeutic interventions. Although wild-type and known variant ChR2s are able to drive light-activated spike trains, their use in potential clinical applications is limited by either low light sensitivity or slow channel kinetics. We present a new variant, calcium translocating channelrhodopsin (CatCh), which mediates an accelerated response time and a voltage response that is ∼70-fold more light sensitive than that of wild-type ChR2. CatCh's superior properties stem from its enhanced Ca2+ permeability. An increase in [Ca2+]i elevates the internal surface potential, facilitating activation of voltage-gated Na+ channels and indirectly increasing light sensitivity. Repolarization following light-stimulation is markedly accelerated by Ca2+-dependent BK channel activation. Our results demonstrate a previously unknown principle: shifting permeability from monovalent to divalent cations to increase sensitivity without compromising fast kinetics of neuronal activation. This paves the way for clinical use of light-gated channels. [ABSTRACT FROM AUTHOR]

The major excitatory neurotransmitter transporter EAAC1 in the mammalian central nervous system is considered a possible target for Chinese herbal medicine. Extracts of Acorus tatarinowii (Schott) were tested for their effects on EAAC1 activity. XENOPUS oocytes with heterologously expressed EAAC1 were used as the model system. Rate of glutamate uptake was determined by means of the isotopic tracer technique. Glutamate-induced current was recorded under a two-electrode voltage clamp. As a highly effective component, alpha-asarone was identified. The rate of glutamate uptake was stimulated by 200 microM of alpha-asarone by about 15 %. In contrast, the same concentration reduced the EAAC1-mediated current by about 35 % at a holding potential of - 60 mV; half maximum inhibition was obtained at about 60 microM. Our experimental data suggest that both stimulation of glutamate uptake and inhibition of EAAC1-mediated current by alpha-asarone could contribute to reduced excitatory activity., (Georg Thieme Verlag KG Stuttgart.New York.)