Mechanisms of the modulation of pacemaker activity by GnRH peptides in the terminal nerve-GnRH neurons.
According to our working hypothesis, the terminal nerve (TN)-gonadotropin releasing hormone (GnRH) system functions as a neuromodulatory system that regulates many long-lasting changes in animal behaviors. We have already shown by using in vitro whole brain preparations of a small fish (dwarf gourami) that the pacemaker activities of TN-GnRH neurons are modulated biphasically by salmon GnRH, which is the same molecular species of GnRH produced by TN-GnRH neurons themselves; the modulation consists of initial transient decrease and late increase of firing frequency. In the present study, we investigated the possible involvement of Ca2+ release from intracellular store and voltage dependent Ca2+ currents in the modulation of pacemaker activities. Pharmacological blockade of Ca2+ release from intracellular stores or apamin-sensitive Ca(2+)-activated K+ current inhibited the initial transient decrease of firing frequency by sGnRH. On the other hand, bath application of Ca2+ channel blockers Ni2+ or La3+ slowed down the pacemaker frequency and attenuated the rate of the late increase of pacemaker frequency by GnRH. Furthermore, voltage-clamp experiments suggested that low-voltage-activated (LVA) Ca2+ current and hihg-voltage-activated (HVA) Ca2+ current were present in the TN-GnRH neurons, and bath application of GnRH shifted the activation threshold of HVA Ca2+ current to more negative potentials. These results suggest that (1) sGnRH induces Ca2+ release from intracellular stores and activates apaminsensitive Ca(2+)-activated K+ current so that it decreases the frequency of pacemaker activity in the initial phase, (2) some kinds of Ca2+ currents contribute to the generation and modulation of pacemaker activities, and (3) HVA Ca2+ current is facilitated by sGnRH so that it increases the frequency of pacemaker activity in the late phase.
Abe
Hideki
H
Misaki Marine Biological Station, Graduate School of Science, University of Tokyo, Kanagawa 238-0225, Japan.
Oka
Yoshitaka
Y
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001683:Biological Clocks / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D004594:Electrophysiology; D005260:Female; D005399:Fishes / Q000502:physiology*; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism
D011966:Receptors, LHRH; D001030:Apamin; D007987:Gonadotropin-Releasing Hormone; D009532:Nickel; D011188:Potassium; D002118:Calcium