TRPC channels are involved in calcium-dependent migration and proliferation in immortalized GnRH neurons.

Abstract: Gonadotropin-releasing hormone (GnRH)-secreting neurons are key regulators of the reproductive behaviour in vertebrates. These neurons show a peculiar migratory pattern during embryonic development, and its perturbations have profound impact on fertility and other related functional aspects. Changes in the intracellular calcium concentration, [Ca²⁺] _i , induced by different extracellular signals, play a central role in the control of neuronal migration, but the available knowledge regarding GnRH neurons is still limited. Our goal was to investigate mechanisms that may be involved in the Ca²⁺ dependence of the migratory behaviour in these neurons. We focused on the “classical” Transient Receptor Potential (TRPC) subfamily of Ca²⁺-permeable cation channels, recently shown to be involved in other aspects of neuronal development. Using GN11 cells, immortalized early stage GnRH neurons, we set to investigate Ca²⁺ signals under basal conditions and in the presence of a well-established motogen, fetal calf serum (FCS), and the effect of pharmacological TRPC agonists and antagonists on Ca²⁺ oscillations, cell motility and proliferation. We have found that a subpopulation of GN11 cells shows spontaneous Ca²⁺ transients and that this activity is increased in the presence of serum. Quantitative real-time PCR showed that transcripts of some TRPC members are expressed in GN11 cells. Interestingly, pharmacological experiments with inhibitors, SKF-96365, lanthanum, anti-TRPC1 antibody, and activators, 1-oleil 2-acetyl-sn-glycerol, of TRPCs suggested that the activation of these channels can account for both the basal Ca²⁺ oscillations and the increased activity in the presence of FCS. Moreover, functional studies using the same pharmacological tools supported their involvement in the control of motility and proliferation. Thus, our data provide evidence for the involvement of Ca²⁺-permeable channels of the TRPC subfamily in the control of functional properties of neurosecretory cells and neuronal motility. [Copyright &y& Elsevier]