Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: Involvement of IDR and ERG K + currents

Agnese Secondo, Anna Pannaccione, Mauro Cataldi, Rossana Sirabella, Luigi Formisano, Gianfranco Di Renzo, Lucio Annunziato

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The role of nitric oxide (NO) in the occurrence of intracellular Ca 2+ concentration ([Ca2+]i) oscillations in pituitary GH3 cells was evaluated by studying the effect of increasing or decreasing endogenous NO synthesis with L-arginine and nitro-L-arginine methyl ester (L-NAME), respectively. When NO synthesis was blocked with L-NAME (1 mM) [Ca2+]i, oscillations disappeared in 68% of spontaneously active cells, whereas 41% of the quiescent cells showed [Ca2+]i oscillations in response to the NO synthase (NOS) substrate L-arginine (10 mM). This effect was reproduced by the NO donors NOC-18 and S-nitroso-N-acetylpenicillamine (SNAP). NOC-18 was ineffective in the presence of the L-type voltage-dependent Ca2+ channels (VDCC) blocker nimodipine (1 μM) or in Ca2+-free medium. Conversely, its effect was preserved when Ca2+ release from intracellular Ca2+ stores was inhibited either with the ryanodine-receptor blocker ryanodine (500 μM) or with the inositol 1,4,5-trisphosphate receptor blocker xestospongin C (3 μM). These results suggest that NO induces the appearance of [Ca2+]i oscillations by determining Ca2+ influx. Patch-clamp experiments excluded that NO acted directly on VDCC but suggested that NO determined membrane depolarization because of the inhibition of voltage-gated K+ channels. NOC-18 and SNAP caused a decrease in the amplitude of slow-inactivating (IDR) and ether-à-go-go-related gene (ERG) hyperpolarization-evoked, deactivating K+ currents. Similar results were obtained when GH3 cells were treated with L-arginine. The present study suggests that in GH3 cells, endogenous NO plays a permissive role for the occurrence of spontaneous [Ca2+]i oscillations through an inhibitory effect on IDR and on I ERG.

Original languageEnglish
JournalAmerican Journal of Physiology - Cell Physiology
Issue number1
Publication statusPublished - Jan 2006


  • Ether-à-go-go-related gene potassium channels
  • Fast-inactivating outward currents
  • Slow-inactivating outward currents
  • Voltage-gated potassium channels

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology


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