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Retinoid receptor-based signaling plays a role in voltage-dependent inhibition of invertebrate voltage-gated Ca 2+ channels

Eric de Hoog, Mark K Lukewich, Gaynor E Spencer

J Biol Chem. 2019 Jun 28;294(26):10076-10093.

PMID: 31048374

Abstract:

The retinoic acid receptor (RAR) and retinoid X receptor (RXR) mediate the cellular effects of retinoids (derivatives of vitamin A). Both RAR and RXR signaling events are implicated in hippocampal synaptic plasticity. Furthermore, retinoids can interact with calcium signaling during homeostatic plasticity. We recently provided evidence that retinoids attenuate calcium current (I Ca) through neuronal voltage-gated calcium channels (VGCCs). We now examined the possibility that constitutive activity of neuronal RXR and/or RAR alters calcium influx via the VGCCs. We found that in neurons of the mollusk Lymnaea stagnalis, two different RXR antagonists (PA452 and HX531) had independent and opposing effects on I Ca that were also time-dependent; whereas the RXR pan-antagonist PA452 enhanced I Ca, HX531 reduced I Ca Interestingly, this effect of HX531 occurred through voltage-dependent inhibition of VGCCs, a phenomenon known to influence neurotransmitter release from neurons. This inhibition appeared to be independent of G proteins and was largely restricted to Cav2 Ca2+ channels. Of note, an RAR pan-antagonist, LE540, also inhibited I Ca but produced G protein-dependent, voltage-dependent inhibition of VGCCs. These findings provide evidence that retinoid receptors interact with G proteins in neurons and suggest mechanisms by which retinoids might affect synaptic calcium signaling.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP188844340 HX531 HX531 188844-34-0 Price
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