Sensitive and Specific Potassium Nanosensors to Detect Epileptic Seizures

Image credit: IBS. Schematic showing the design of the K+ nanosensor. K+ indicators are incorporated inside the nanopores. The thin K+-specific filter membrane on the surface of the nanopores allows only K+ to be internalized. b-c, Chemical structure of the filter membrane. d-e, Schematic illustrations showing the hydration shells on potassium (K+ in red) and sodium ions (Na+ in purple) and sodium ions in deionized water. f-g, Schematic illustrations and calculated binding energy of the interactions between the filter membrane cavity and K+/Na+

Researchers at the Center for Nanoparticle Research, within the Institute for Basic Science (IBS, South Korea) in collaboration with collaborators at Zhejiang University, China, have reported a highly sensitive and specific nanosensor that can monitor dynamic changes of potassium ions in mice undergoing epileptic seizures, indicating their intensity and origin in the brain.

Epilepsy is a central nervous system disorder accompanied by abnormal brain activity, causing seizures or periods of unusual behavior, sensations, and sometimes loss of awareness. If epileptic seizures last for 30 minutes or longer, they can cause permanent brain damage or even death. The need of technologies to evaluate the degree of abnormal electrical activity associated with epilepsy is well known.

One of the main investigation targets is the potassium (K+) ion. This ion affects the difference in electric potential between the interior and exterior membranes of the neurons, and impacts the neuronal intrinsic excitability and synaptic transmission. Despite the significant efforts to improve the selectivity of K+ sensors, they are still far from satisfactory because currently available optical reporters are not capable of detecting small changes in potassium ions, in particular, in freely moving animals. Furthermore, they are susceptible to interference from sodium ions because Na+ influx is shortly followed by K+ efflux when impulses pass along the membrane of a nerve cell. In this study published in Nature Nanotechnology, the researchers report a highly sensitive and selective K+ nanosensor that can monitor the changes of K+ in the different parts of the brains of freely moving mice.

The new nanosensor is created with porous silica nanoparticles shielded by an ultrathin potassium-permeable membrane that is very similar to the potassium channel in brain cells. The size of the pores allows only K+ to diffuse in and out, reaching a detection limit as low as 1.3 micromolar. This allows the specific readout of sub-millimolar variations of extracellular K+ and the spatial mapping of this ion in the brain.