Nanoelectropulse Induced Changes in Cell Excitability - A New Approach for Neuromodulation
Abstract
This multidisciplinary project has been to explore the potential for nanosecond-duration electric pulses (NEPs) to serve as a safe and potentially non-invasive approach for altering neural cell excitability, with the overall objective of developing new ways to enhance human performance. Our strategy combined experimental and computational approaches to elucidate how very short duration (less than 10 ns in duration) electric pulses of high intensity (>1 megavolt-per-meter; MV/m) alter the excitability of isolated bovine adrenal chromaffin cells, a leading non-transformed model of neurosecretion. Crucial to the success of the project was designing and fabricating a setup to record membrane currents as soon as possible following the delivery of a NEP. Using this setup we obtained results consistent with the hypothesis originally proposed, namely that NEPs cause membrane depolarization by a novel mechanism, influx of Na+ through membrane 'electropores' or 'nanopores'. This in turn causes activation of voltage-gated Ca2+ channels and a rise in [Ca2+]i that is of sufficient magnitude to evoke Ca2+- dependent neurosecretion. We also unexpectedly found that Transient Receptor Potential or TRP channels serve as another pathway of Na+ entry into chromaffin cells exposed to NEPs, indicating that these channels are an important membrane target of NEPs that can affect cell excitability. Other novel effects of NEPs on chromaffin cell excitability that were revealed include differential electric field (E-field) and pulse-number effects on voltage-gated Na+ and K+ currents.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 12, 2019
- Accession Number
- AD1096663
Entities
People
- Gale Craviso
Organizations
- University of Nevada, Reno