Author(s): Roth CC, Tolstykh GP, Payne JA, Kuipers MA, Thompson GL
The persistent influx of ions through nanopores created upon cellular exposure to nanosecond pulse electric fields (nsPEF) could be used to modulate neuronal function. One ion, calcium (Ca(2+)), is important to action potential firing and regulates many ion channels. However, uncontrolled hyper-excitability of neurons leads to Ca(2+) overload and neurodegeneration. Thus, to prevent unintended consequences of nsPEF-induced neural stimulation, knowledge of optimum exposure parameters is required. We determined the relationship between nsPEF exposure parameters (pulse width and amplitude) and nanopore formation in two cell types: rodent neuroblastoma (NG108) and mouse primary hippocampal neurons (PHN). We identified thresholds for nanoporation using Annexin V and FM1-43, to detect changes in membrane asymmetry, and through Ca(2+) influx using Calcium Green. The ED50 for a single 600 ns pulse, necessary to cause uptake of extracellular Ca(2+), was 1.76 kV/cm for NG108 and 0.84 kV/cm for PHN. At 16.2 kV/cm, the ED50 for pulse width was 95 ns for both cell lines. Cadmium, a nonspecific Ca(2+) channel blocker, failed to prevent Ca(2+) uptake suggesting that observed influx is likely due to nanoporation. These data demonstrate that moderate amplitude single nsPEF exposures result in rapid Ca(2+) influx that may be capable of controllably modulating neurological function.
Referred From: https://www.ncbi.nlm.nih.gov/pubmed/23532338
Author(s): Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, et al.
Author(s): Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, et al.
Author(s): Fouladi M, Hunt DL, Pollack IF, Dueckers G, Burger PC, et al.
Author(s): Nelson D, Nelson J, Davis D, Chang C, Griffins T, et al.
Author(s): Parvez T
Author(s): Reese TS, Karnovsky MJ
Author(s): Kreuter J
Author(s): Kreuter J.
Author(s): Delpassand ES, Samarghandi A, Zamanian S, Wolin EM, Hamiditabar M, et al.
Author(s): Humm JL, Sartor O, Parker C, Bruland OS, Macklis R
Author(s): Shore ND
Author(s): Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, et al.
Author(s): Chanda N, Kan P, Watkinson LD, Shukla R, Zambre A, et al.
Author(s): Bhattacharyya S, Bhattacharya R, Curley S, McNiven MA, Mukherjee P
Author(s): Arvizo RR, Miranda OR, Thompson MA, Pabelick CM, Bhattacharya R, et al.
Author(s): Arvizo RR, Miranda OR, Moyano DF, Walden CA, Giri K, et al.
Author(s): Bhattacharyya S, Singh RD, Pagano R, Robertson JD, Bhattacharya R, et al.
Author(s): Kudgus RA, Walden CA, McGovern RM, Reid JM, Robertson JD, et al.
Author(s): Kennel SJ, Chappell LL, Dadachova K, Brechbiel MW, Lankford TK, et al.
Author(s): McLaughlin MF, Robertson D, Pevsner PH, Wall JS, Mirzadeh S, et al.
Author(s): Woodward J, Kennel SJ, Stuckey A, Osborne D, Wall J, et al.
Author(s): McLaughlin MF, Woodward J, Boll RA, Wall JS, Rondinone AJ, et al.
Author(s): Miller DC, Koslow M, Budzilovich GN, Burstein DE
Author(s): Joshi RP, Hu Q
Author(s): Joshi RP, Schoenbach KH