Partial characterization of K+-induced increase in [Ca2+]cyt and GnRH release in GT1-7 neurons

Martin A. Javors, Thomas S. King, Xiaoying Chang, Nancy A. Klein, Robert S. Schenken

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Secretion of pituitary gonadotropins is regulated centrally by the hypothalamic decapeptide gonadotropin releasing hormone (GnRH). Using the immortalized hypothalamic GT1-7 neuron, we characterized pharmacologically the dynamics of cytosolic Ca2+ and GnRH release in response to K+-induced depolarization of GT1-7 neurons. Our results showed that K+ concentrations from 7.5 to 60 mM increased [Ca2+]cyt in a concentration-dependent manner. Resting [Ca2+]cyt in GT1-7 cells was determined to be 69.7 ± 4.0 nM (mean ± S.E.M.; n = 69). K+-induced increases in [Ca2+]cyt ranged from 58.2 nM at 7.5 mM [K+] to 347 nM at 60 mM [K+]. K+-induced GnRH release ranged from about 10 pg/ml at 7.5 mM [K+] to about 60 pg/ml at 45 mM [K+]. K+-induced increases in [Ca2+]cyt and GnRH release were enhanced by 1 μM BayK 8644, an L-type Ca2+ channel agonist. The BayK enhancement was completely inhibited by 1 μM nimodipine, an L-type Ca2+ channel antagonist. Nimodipine (1 μM) alone partially inhibited K+-induced increases in [Ca2+]cyt and GnRH release. Conotoxin (1 μM) alone had no effect on K+-induced GnRH release or [Ca2+]cyt, but the combination of conotoxin (1 μM) and nimodipine (1 μM) inhibited K+-induced increase in [Ca2+]cyt significantly more (p < 0.02) than nimodipine alone, suggesting that N-type Ca2+ channels exist in GT1-7 neurons and may be part of the response to K+. The response of [Ca2+]cyt to K+ was linear with increasing [K+] whereas the response of GnRH release to increasing [K+] appeared to be saturable. K+-induced increase in [Ca2+]cyt and GnRH release required extracellular [Ca2+]. These experiments suggest that voltage dependent N- and L-type Ca2+ channels are present in immortalized GT1-7 neurons and that GnRH release is, at least in part, dependent on these channels for release of GnRH.

Original languageEnglish (US)
Pages (from-to)49-54
Number of pages6
JournalBrain Research
Volume694
Issue number1-2
DOIs
StatePublished - Oct 2 1995

Keywords

  • BayK 8644
  • Calcium channel
  • Conotoxin
  • GT1-7 neuron
  • GnRH
  • Hypothalamus
  • Nimodipine
  • Voltage-dependent Ca channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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