A central question in adenohypophyseal cell physiology concerns the role of transmembrane ionic fluxes in the initiation of hormone secretion process. In the current report we investigated the effects of the growth hormone (GH) secretagogues ghrelin and GH-releasing peptide-6 (GHRP-6) on the regulation of the functional expression of voltage-gated Na⁺ channels using the tumoral somatotrope GC cell line as a model. Cells were cultured either under control conditions or in presence of the GH secretagogues (GHS) for 96 h, and Na⁺ currents (I_Na) were characterized in whole-cell patch-clamp experiments. GHS treatment significantly increased I_Na density in a dose-dependent manner. The effects of GHRP-6 were accompanied by an augment in conductance without changes in the kinetics and the voltage dependence of the currents, suggesting an increase in the number of channels in the cell membrane. Sustained inhibition of L-type Ca²⁺ channel activity decreased I_Na density and prevented the effects of the GHS, while long-term exposure to a L-channel agonist increased I_Na density and enhanced the actions of GHRP-6, indicating that Ca²⁺ entry through these channels play a role in the regulation of Na⁺ channel expression. Likewise, GHRP-6 failed to enhance Na⁺ channel expression in the presence of membrane-permeable inhibitors of protein kinases A and C, as well as the Ca²⁺/CaM-dependent kinase II. Conversely, treatment with a cAMP analog or a PKC activator enhanced both basal and GHS-induced secretion of GH measured by ELISA, suggesting that GHRP-6 acting through the GHS receptor and different signaling pathways enhances Na⁺ channel membrane expression which favors hormone release from GC somatotropes.