Novel synthetic sulfoglycolipid IG20 facilitates exocytosis in chromaffin cells through the regulation of sodium channels

Abstract

In searching for druggable synthetic lipids as potential modulators of synaptic transmission and plasticity, we synthesized sulfoglycolipid IG20 that stimulates neuritic outgrowth. Here we have explored its effects on ion channels and exocytosis in bovine chromaffin cells (BCCs). IG20 augmented the rate of basal catecholamine release. Such effect did not depend on Ca2+ mobilization from intracellular stores; rather, IG20-elicited secretion entirely dependent on Ca2+ entry through Lsubtype voltage-activated Ca2+ channels. Those channels were recruited by cell depolarization mediated by IG20 likely through its ability to enhance the recruitment of Na+ channels at more hyperpolarizing potentials. Confocal imaging with fluorescent derivative IG20-NBD revealed its rapid incorporation and confinement into the plasmalemma, supporting the idea that IG20 effects are exerted through a plasmalemmal-delimited mechanism. Thus, synthetic IG20 seems to mimic several physiological effects of endogenous lipids such as regulation of ion channels, Ca2+ signaling, and exocytosis. Therefore, sulfoglycolipid IG20 may become a pharmacological tool to investigate 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