Intercommunication between Voltage-Gated Calcium Channels and Estrogen Receptor/Estrogen Signaling: Insights into Physiological and Pathological Conditions

Abstract

Voltage-gated calcium channels (VGCCs) and estrogen receptors are important cellular proteins that have been shown to interact with each other across varied cells and tissues. Estrogen hormone, the ligand for estrogen receptors, can also exert its effects independent of estrogen receptors that collectively constitute non-genomic mechanisms. Here, we provide insights into the VGCC regulation by estrogen and the possible mechanisms involved therein across several cell types. Notably, most of the interaction is described in neuronal and cardiovascular tissues given the importance of VGCCs in these electrically excitable tissues. We describe the modulation of various VGCCs by estrogen known so far in physiological conditions and pathological conditions. We observed that in most in vitro studies higher concentrations of estrogen were used while a handful of in vivo studies used meager concentrations resulting in inhibition or upregulation of VGCCs, respectively. There is a need for more relevant physiological assays to study the regulation of VGCCs by estrogen. Additionally, other interacting receptors and partners need to be identified that may be involved in exerting estrogen receptor-independent effects of estrogen.

Keywords: L-type calcium channels; T-type calcium channels; calcium influx; estrogen; estrogen receptor signaling; voltage-gated calcium channels.

Figure 1

Overview of estrogenic modulation of VGCCs in physiology and pathology. Left: in physiological conditions, estrogen/ER activation modulates the calcium influx via VGCCs which contributes to various physiological functions. Right: estrogen/ER activation modulates the calcium influx via VGCCs which is observed in various disease conditions. However, whether this modulation causes the pathology or is merely a consequence requires further investigation.