Premium
Novel synthetic sulfoglycolipid IG 20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels
Author(s) -
CrespoCastrillo Andrea,
Punzón Eva,
Pascual Ricardo,
Maroto Marcos,
Padín Juan Fernando,
GarcíaÁlvarez Isabel,
Nanclares Carmen,
RuizPascual Lucía,
Gandía Luis,
FernándezMayoralas Alfonso,
García Antonio G.
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13357
Subject(s) - exocytosis , chromaffin cell , sodium channel , microbiology and biotechnology , chemistry , sodium , neuroscience , biology , secretion , biochemistry , adrenal medulla , catecholamine , organic chemistry
In search of druggable synthetic lipids that function as potential modulators of synaptic transmission and plasticity, we synthesized sulfoglycolipid IG 20, which stimulates neuritic outgrowth. Here, we have explored its effects on ion channels and exocytosis in bovine chromaffin cells. IG 20 augmented the rate of basal catecholamine release. Such effect did not depend on Ca 2+ mobilization from intracellular stores; rather, IG 20‐elicited secretion entirely dependent on Ca 2+ entry through L‐subtype voltage‐activated Ca 2+ channels. Those channels were recruited by cell depolarization mediated by IG 20 likely through its ability to enhance the recruitment of Na + channels at more hyperpolarizing potentials. Confocal imaging with fluorescent derivative IG 20‐ NBD revealed its rapid incorporation and confinement into the plasmalemma, supporting the idea that IG 20 effects are exerted through a plasmalemmal‐delimited mechanism. Thus, synthetic IG 20 seems to mimic several physiological effects of endogenous lipids such as regulation of ion channels, Ca 2+ signaling, and exocytosis. Therefore, sulfoglycolipid IG 20 may become a pharmacological tool for investigating the role of the lipid environment on neuronal excitability, ion channels, neurotransmitter release, synaptic efficacy, and neuronal plasticity. It may also inspire the synthesis of druggable sulfoglycolipids aimed at increasing synaptic plasticity and efficacy in neurodegenerative diseases and traumatic brain–spinal cord injury.The novel synthetic sulfoglycolipid IG20 mimics several physiological effects of endogenous lipids such as regulation of ion channels, Ca 2+ signaling, and exocytosis. This profile may eventually drive enhanced synaptic plasticity and efficacy.