Gamma-aminobutyric acid and glutamate differentially regulate intracellular calcium concentrations in mouse gonadotropin-releasing hormone neurons.
Multiple factors regulate the activity of the GnRH neurons responsible for controlling fertility. Foremost among neuronal inputs to GnRH neurons are those using the amino acids glutamate and gamma-aminobutyric acid (GABA). The present study used a GnRH-Pericam transgenic mouse line, enabling live cell imaging of intracellular calcium concentrations ([Ca(2+)](i)) to evaluate the effects of glutamate and GABA signaling on [Ca(2+)](i) in peripubertal and adult mouse GnRH neurons. Activation of GABA(A), N-methyl-d-aspartate, or alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate acid (AMPA) receptors was found to evoke an increase in [Ca(2+)](i), in subpopulations of GnRH neurons. Approximately 70% of GnRH neurons responded to GABA, regardless of postnatal age or sex. Many fewer (approximately 20%) GnRH neurons responded to N-methyl-d-aspartate, and this was not influenced by postnatal age or sex. In contrast, about 65% of adult male and female GnRH neurons responded to AMPA compared with about 14% of male and female peripubertal mice (P < 0.05). The mechanisms underlying the ability of GABA and AMPA to increase [Ca(2+)](i) in adult GnRH neurons were evaluated pharmacologically. Both GABA and AMPA were found to evoke [Ca(2+)](i) increases through a calcium-induced calcium release mechanism involving internal calcium stores and inositol-1,4,5-trisphosphate receptors. For GABA, the initial increase in [Ca(2+)](i) originated from GABA(A) receptor-mediated activation of L-type voltage-gated calcium channels, whereas for AMPA this appeared to involve direct calcium entry through the AMPA receptor. These observations show that all of the principal amino acid receptors are able to control [Ca(2+)](i) in GnRH neurons but that they do so in a postnatal age- and intracellular pathway-specific manner.
Centre for Neuroendocrinology, Department of Physiology, University of Otago School of Medical Sciences, Dunedin 9054, New Zealand.
Stephanie
S
Constantin
Christine L
CL
Jasoni
Brandon
B
Wadas
Allan E
AE
Herbison
D000375:Aging / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D005260:Female; D018698:Glutamic Acid / Q000494:pharmacology*; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D042541:Intracellular Space / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018091:Receptors, AMPA; D007987:Gonadotropin-Releasing Hormone; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium