It is well established that pituitary somatotropes fire spontaneous action potentials (SAP) which generate Ca2+ signals of sufficient amplitude to trigger growth hormone (GH) release. It is also known that ghrelin and synthetic GH-releasing peptides (GHRPs) stimulate GH secretion, though the mechanisms involved remain unclear. In the current report, we show that the chronic (96 h) treatment with ghrelin and GHRP-6 increases the firing frequency of SAP in the somatotrope GC cell line. This action is associated with a significant increase in whole-cell inward current density. In addition, long-term application of Na+ or L-type Ca2+ current antagonists decreases GHRP-6-induced release of GH, indicating that the ionic currents that give rise to SAP play important roles for hormone secretion in the GC cells. Together, our results suggest that ghrelin and GHPR-6 may increase whole-cell inward current density thereby enhancing SAP firing frequency and facilitating GH secretion from GC somatotropes. (c) 2007 Published by Elsevier Inc.