Two slow calcium-activated afterhyperpolarization currents control burst firing dynamics in gonadotropin-releasing hormone neurons.
Gonadotropin-releasing hormone (GnRH) neurons release GnRH in a pulsatile manner to control fertility in all mammals. The mechanisms underlying burst firing in GnRH neurons, thought to contribute to pulsatile GnRH release, are not yet understood. Using minimally invasive, dual electrical-calcium recordings in acute brain slices from GnRH-Pericam transgenic mice, we find that the soma/proximal dendrites of GnRH neurons exhibit long-duration (approximately 10 s) calcium transients that are perfectly synchronized with their burst firing. These transients were found to be generated by calcium entry through voltage-dependent L-type calcium channels that was amplified by inositol-1,4,5-trisphosphate receptor-dependent store mechanisms. Perforated-patch current- and voltage-clamp electrophysiology coupled with mathematical modeling approaches revealed that these broad calcium transients act to control two slow afterhyperpolarization currents (sI(AHP)) in GnRH neurons: a quick-activating apamin-sensitive sI(AHP) that regulates both intraburst and interburst dynamics, and a slow-onset UCL2077-sensitive sI(AHP) that regulates only interburst dynamics. These observations highlight a unique interplay between electrical activity, calcium dynamics, and multiple calcium-regulated sI(AHP)s critical for shaping GnRH neuron burst firing.
Lee
Kiho
K
Centre for Neuroendocrinology and Department of Physiology, University of Otago, Dunedin 9054, New Zealand.
Duan
Wen
W
Sneyd
James
J
Herbison
Allan E
AE
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001596:Benzylamines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology
C549620:3-(triphenylmethylaminomethyl)pyridine; D001596:Benzylamines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011725:Pyridines; D001030:Apamin; D007987:Gonadotropin-Releasing Hormone; D002118:Calcium
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