Optocapacitance-Mediated Responses of Excitable Cells: New Developments

Abstract

Optocapacitance is a technique whereby flash illumination quickly changes membrane capacitance to elicit action potentials (APs) in unmodified (not genetically engineered) excitable cells. Spherical 20-nm gold nanoparticles (AuNPs) interfaced with the plasma membrane serve as light absorbers to induce AP generation in response to 1-ms, 100 μJ, 532-nm laser pulses. Light absorption by the AuNP produces localized heating that changes local temperature by <2⁰C. This increases membrane capacitance, and a resulting depolarizing membrane current (VdC/dt; proportional to the rate of temperature change; Nat. Commun., 2012;3:736) induces opening of voltage-gated sodium channels and thus AP initiation in neurons (Neuron, 2015;86:207-17). Here we present new findings obtained from dorsal root ganglion (DRG) cells, by varying the flash wavelength, light-absorbing particle, and flash duration. Using cylindrical AuNPs (nanorods; 25x94 nm; plasmon absorbance peak at ∼780 nm), a 1-ms, 20 μJ, 785-nm laser pulse was sufficient to elicit APs. A single 1-2 μm graphite particle placed on the DRG cell induced AP generation upon delivery of a 532-nm laser flash of 4 ns duration and 47 nJ energy, representing 130-fold less energy than the 6.2 μJ needed with a 0.5-ms laser pulse. With AuNPs, reduction in flash duration similarly decreased the flash energy required for AP generation. Our data demonstrate the use of near-infrared flashes that penetrate deeper into tissue than green light to elicit APs with light. They also indicate that, in addition to gold and mesoporous silicon (Nat. Mater., 2016;15:1023-30), graphite can enable optocapacitive AP generation. The data furthermore show that, with ∼nanosecond flash durations, APs can be elicited by flashes of ∼nano-Joule energy, i.e., in the range of those used in optogenetic approaches. Support: NIH grants R21-EY023430, R01-GM030376, and the Beckman Initiative for Macular Research.