Effects of 17beta-estradiol and IGF-1 on L-type voltage-activated and stretch-activated calcium currents in cultured rat cortical neurons

Calcium transport pathways are key factors for understanding how changes in the cytoplasmic calcium concentration are associated with neuroprotection because calcium is involved in the onset of death signaling in neurons. This study characterized the effects of 17β-estradiol and IGF-1 on voltage-activated and stretch-activated calcium channels in rat cultured cortical neurons. The whole-cell patch-clamp technique, using a voltage steps protocol or by applying positive pressure into the micropipette, was used on 7-10 day cultured neurons from a Wistar rat cortex, and pharmacological characterization was performed on these neurons. Both 17β-estradiol and IGF-1 inhibited the currents mediated by L-type voltage-activated calcium channels, although the IGF-1 effects were lower than those of 17β-estradiol. The effect of both hormones together was greater than the sum of the effects of the individual agents. Unlike IGF-1, 17β-estradiol decreased the current mediated by stretch-activated channels. The inhibition of the classical receptors of these hormones did not affect the results. Both hormones regulate voltage-activated calcium channels in a synergistic way, but only 17β-estradiol has an inhibitory effect on stretch-activated calcium channels. These effects are not mediated by classical receptors and may be relevant to the neuroprotective effects of both hormones because they diminish calcium entry into the neuron and decrease the possibility for the onset of apoptotic signaling.