Frequency-dependent interaction of ultrashort E-fields with nociceptor membranes and proteins

We examined the influence of ultrashort pulses (USP) on sensory neurons. Single and high frequency bursts of 12 ns E‐fields were presented to rat skin nociceptors that expressed distinct combinations of voltage‐sensitive proteins. A single E‐field pulse produced action potentials in all nociceptor subtypes at a critical threshold (E_c) of 403 V/cm. When configured into high frequency bursts, USP charge integrated to reduce the action potential threshold in a frequency and burst duration‐dependent manner with E_c as low as 16 V/cm (4000 Hz, 25 ms burst). There was no evidence of electroporation at field intensities near the E_c for nociceptor activation. USP bursts activated a late, persistent Ca⁺⁺ flux that was identified as a dantrolene‐sensitive Ca⁺⁺‐induced Ca⁺⁺ release (CICR). Influx of Ca⁺⁺ into the cell was required for the CICR and resulted in a reduction of the single pulse E_c by about 50%. Bioelectromagnetics 32:148–163, 2011. © 2010 Wiley‐Liss, Inc.