Open AccessParadoxical effects on voltage-gated Na+ conductance in adrenal chromaffin cells by twin vs single high intensity nanosecond electric pulses
Author(s) -
Lisha Yang,
Sophia Pierce,
Indranil Chatterjee,
Gale L. Craviso,
Normand Leblanc
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0234114
Subject(s) - conductance , membrane potential , electric field , nanosecond , biophysics , chemistry , electrophysiology , lipid raft , endocrinology , medicine , physics , cholesterol , biology , condensed matter physics , optics , laser , quantum mechanics
We previously reported that a single 5 ns high intensity electric pulse (NEP) caused an E-field-dependent decrease in peak inward voltage-gated Na + current (I Na ) in isolated bovine adrenal chromaffin cells. This study explored the effects of a pair of 5 ns pulses on I Na recorded in the same cell type, and how varying the E-field amplitude and interval between the pulses altered its response. Regardless of the E-field strength (5 to 10 MV/m), twin NEPs having interpulse intervals ≥ than 5 s caused the inhibition of TTX-sensitive I Na to approximately double relative to that produced by a single pulse. However, reducing the interval from 1 s to 10 ms between twin NEPs at E-fields of 5 and 8 MV/m but not 10 MV/m decreased the magnitude of the additive inhibitory effect by the second pulse in a pair on I Na . The enhanced inhibitory effects of twin vs single NEPs on I Na were not due to a shift in the voltage-dependence of steady-state activation and inactivation but were associated with a reduction in maximal Na + conductance. Paradoxically, reducing the interval between twin NEPs at 5 or 8 MV/m but not 10 MV/m led to a progressive interval-dependent recovery of I Na , which after 9 min exceeded the level of I Na reached following the application of a single NEP. Disrupting lipid rafts by depleting membrane cholesterol with methyl-β-cyclodextrin enhanced the inhibitory effects of twin NEPs on I Na and ablated the progressive recovery of this current at short twin pulse intervals, suggesting a complete dissociation of the inhibitory effects of twin NEPs on this current from their ability to stimulate its recovery. Our results suggest that in contrast to a single NEP, twin NEPs may influence membrane lipid rafts in a manner that enhances the trafficking of newly synthesized and/or recycling of endocytosed voltage-gated Na + channels, thereby pointing to novel means to regulate ion channels in excitable cells.