Growth hormone-releasing hormone augments voltage-gated Na+ current in cultured rat pituitary cells.
The effect of human growth hormone-releasing hormone (hGHRH), a potent stimulator of adenylate cyclase in somatotrophs on the voltage-gated sodium current was determined by perforated patch clamp of cultured rat somatotrophs The amplitude of the voltage-gated sodium current was augmented by 65.3 +/- 20.6% (mean +/- SE, n = 7) by 10 nM hGHRH. This augmentation was reversibly blocked by 10 microM H-89 a specific inhibitor for adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase. The membrane-permeant analogue of cAMP, dibutyryl cAMP (5 mM), also augmented the voltage-gated sodium current by 39.6 +/- 7.4% (n = 10). There were no effects of hGHRH or dibutyryl cAMP on steady-state inactivation of the sodium current. In contrast, in the whole cell configuration of patch clamp, no augmentation of the sodium current was observed by hGHRH or by the membrane-permeant analogue of cAMP. These results suggest that hGHRH augments the peak amplitude of the voltage-gated sodium current in rat somatotrophs via phosphorylation by cAMP-dependent protein kinase. For this augmentation, the intracellular environment must be kept relatively intact.
Kato
M
M
Department of Physiology, Gunma University, Maebashi, Japan.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D004553:Electric Conductivity; D004594:Electrophysiology; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D015640:Ion Channel Gating; D007700:Kinetics; D008297:Male; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000502:physiology*; D013004:Somatostatin / Q000494:pharmacology; D013997:Time Factors
D013004:Somatostatin; D003994:Bucladesine; D013007:Growth Hormone-Releasing Hormone; D012964:Sodium