Growth hormone-releasing hormone decreases voltage-gated potassium currents in GH4C1 cells

R. Xu, I. J. Clarke, S. Chen, Chen Chen

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The electrophysiological properties of anterior pituitary somatotropes integrally involve the function of voltage-gated K+ currents. In this study, we have used GH4C1 cell lines to investigate the effect of human GHRH on voltage-gated K+ currents. Because of a clear 'rundown' of the K+ current with classic whole cell recording (WCR) without ATP in pipette solution, nystatin-perforated WCR was the major recording configuration used. Using a low Ca2+ (0.5 mM) bath solution containing Co2+ (1 mM) and TTX (1 μM), GH4 cells predominantly exhibited an outward delayed rectifier K+ current (I(K)). Local application of growth hormone releasing hormone (GHRH) (100 nM) reversibly reduced the amplitude of the K+ currents (to 83% of control). There was no effect of GHRH on the activation curve of the K+ current and no difference observed using 2.5 mM Ca2+ or low Ca2+ (0.5 mM Ca2+ + 1 mM Co2+) bath solutions. Under the condition of low Ca2+ bath solution, the application of apamin (1 μM) or charybdotoxin (1 μM), two specific blockers of the Ca2+-activated K+ current, did not alter the K+ current or the response to GHRH. This reduction in the K+ current by GHRH was also observed with classic WCR with a pipette solution containing ATP (2 mM). The GHRH-induced reduction in the K+ current was completely abolished by the presence of GDP-β-s (500 μM) in the pipette solution or by addition of PKC inhibitors, calphostin C (100 nM) and chelerythrine (1 μM), in bath solution. Inhibitor for cAMP-PKA system (Rp-cAMP and H89) did not affect the K+ current response to GHRH. These results suggest that GHRH reduces the voltage-gated K+ current in GH4C1 cells, a response that is mediated by G-proteins and PKC system but not by cAMP-PKA system. The reduction in the K+ current may partially contribute to the GHRH-stimulated growth hormone (GH) secretion.

Original languageEnglish
Pages (from-to)147-157
Number of pages11
JournalJournal of Neuroendocrinology
Issue number2
Publication statusPublished - 28 Feb 2000
Externally publishedYes


  • Growth hormone
  • K channels
  • Patch-clamp
  • Pituitary

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