Effects of Estradiol and IGF-1 on the Sodium Calcium Exchanger in Rat Cultured Cortical Neurons

Abstract

The Na(+)/Ca(2+) exchanger (NCX) is an important bidirectional transporter of calcium in neurons and has been shown to be involved in neuroprotection. Calcium can activate a number of cascades that can result in apoptosis and cell death, and NCX is a key factor in regulating the cytoplasmic concentration of this ion. 17-β-estradiol and insulin-like growth factor 1 (IGF-1) are known neuroprotective hormones with interacting mechanisms and effects on intracellular calcium; however, their relationship with the NCX has not been explored. In this article, the effects of these two hormones on neuronal NCX were tested using the whole-cell patch clamp technique on rat primary culture neurons. Both 17-β-estradiol and IGF-1 produced an increase in the NCX-mediated inward current and a decrease in the NCX-mediated outward current. However, the IGF-1 effect was lower than that of 17-β-estradiol, and the effect of both agents together was greater than the sum of each agent alone. Neither of the agents affected the pattern of regulation by extracellular or intrapipette calcium. Inhibitors of the IGF-1 and 17-β-estradiol receptors and inhibitors of the main signaling pathways failed to change the observed effects, indicating that these actions were not mediated by the classical receptors of these hormones. These effects on the NCX could be a mechanism explaining the neuroprotective actions of 17-β-estradiol and IGF-1, and these findings could help researchers to understand the role of the NCX in neuroprotection.

Stroke Neuroprotection: Oestrogen and Insulin‐Like Growth Factor‐1 Interactions and the Role of Microglia

“…In the case of the sodium calcium exchanger in cortical neurones, however, combining the two compounds enhanced the independent action of oestrogen and IGF‐1. Furthermore, this action was independent of the classical receptors because neither oestrogen, nor IGF‐1 receptor antagonists could prevent these effects . Similarly, both oestrogen and IGF‐1 enhance neurogenesis in the dentate gyrus of the hippocampus and the hormones appear to have a synergistic effect.…”

Estrogen-IGF-1 interactions in neuroprotection: Ischemic stroke as a case study

“…In the case of the sodium calcium exchanger in cortical neurons, however, combining the two compounds enhanced the independent action of 17b-estradiol and IGF-1. Furthermore, this action was independent of the classical receptors, since neither estrogen nor IGF-1 receptor antagonists could prevent these effects (Sanchez et al, 2011). Similarly, both estrogen and IGF-1 enhance neurogenesis in the dentate gyrus of the hippocampus and the hormones appear to have a synergistic effect.…”

17β-Estradiol Reduces Nitric Oxide Production in the Guinea Pig Cochlea

“…Furthermore, 17β-estradiol produced an increase in the Na + -Ca 2 + exchanger-mediated inward current and a decrease in the outward current in rat cultured primary cortical neurons. The blockade resulted in a decreased Ca 2 + infl ux and increased Ca 2 + effl ux [ 41 ] . In the vertebrate cochlea, the Na + -Ca 2 + exchanger was identifi ed in the outer hair cells [ 42 ] .…”