Background: Neurosteroids form the unique group because of their dual mechanism of
action. Classically, they bind to specific intracellular and/or nuclear receptors, and next modify
genes transcription. Another mode of action is linked with the rapid effects induced at the plasma
membrane level within seconds or milliseconds. The key molecules in neurotransmission are
calcium ions, thereby we focus on the recent advances in understanding of complex signaling
crosstalk between action of neurosteroids and calcium-engaged events.
Methods: Short-time effects of neurosteroids action have been reviewed for GABAA receptor
complex, glycine receptor, NMDA receptor, AMPA receptor, G protein-coupled receptors and
sigma-1 receptor, as well as for several membrane ion channels and plasma membrane enzymes,
based on available published research.
Results: The physiological relevance of neurosteroids results from the fact that they can be
synthesized and accumulated in the central nervous system, independently from peripheral sources.
Fast action of neurosteroids is a prerequisite for genomic effects and these early events can
significantly modify intracellular downstream signaling pathways. Since they may exert either
positive or negative effects on calcium homeostasis, their role in monitoring of spatio-temporal
Ca2+ dynamics, and subsequently, Ca2+-dependent physiological processes or initiation of
pathological events, is evident.
Conclusion: Neurosteroids and calcium appear to be the integrated elements of signaling systems
in neuronal cells under physiological and pathological conditions. A better understanding of
cellular and molecular mechanisms of nongenomic, calcium-engaged neurosteroids action could
open new ways for therapeutic interventions aimed to restore neuronal function in many
neurological and psychiatric diseases.