Kisspeptin-evoked calcium signals in isolated primary rat gonadotropin- releasing hormone neurones.
Kroll. Heike H; Bolsover. Stephen S; Hsu. Judith J; Kim. Soo-Hyun SH; Bouloux. Pierre-Marc PM
Key Findings
- 100 nM kisspeptin-10 causes a sustained rise in calcium inside isolated rat GnRH neurons.
- Blocking sodium channels with tetrodotoxin cuts the calcium rise by about 30%, indicating a sodium‑action‑potential component.
- Inhibiting TRP‑type calcium entry with SKF96365 reduces the signal by 76%, and removing external calcium eliminates it entirely, showing the main pathway is extracellular calcium influx through non‑voltage channels.
Practical Outcomes
- For biohackers, this research confirms that kisspeptin influences hormone release via calcium influx, but it doesn’t provide a clear dosing or supplementation protocol. It suggests that any future attempts to modulate reproductive hormones with kisspeptin would need to consider calcium channel activity, yet at present the findings are mainly mechanistic and not directly actionable.
Summary
The study shows that kisspeptin-10 makes certain brain cells that control reproductive hormones (GnRH neurons) take up more calcium. Most of this calcium comes in through channels that don’t need electrical spikes, while a smaller part comes from voltage‑gated channels that are triggered by sodium spikes.
Abstract
Kisspeptin and its cognate receptor GPR54 are the central driving forces in the hypothalamus-pituitary-gonadal axis essential for sexual maturation and reproduction. Kisspeptin/GPR54 signalling stimulates gonadotropin-releasing hormone (GnRH) neurones and induces pulsatile GnRH release. The molecular signalling pathway by which kisspeptin stimulates GnRH neurones is currently under investigation. Primary GnRH neurones were isolated from young adult rats and loaded with the calcium indicator Fura Red. Cytosolic calcium was measured while the cells were stimulated with kisspeptin. GnRH neurones show a maintained increase of cytosolic calcium upon stimulation with 100 nM kisspeptin-10. The calcium elevation was inhibited 30% by 1 μM tetrodotoxin, a voltage-gated sodium channel blocker, and 76% by 30 μM SKF96365, an inhibitor of receptor-mediated calcium entry. Furthermore, removal of extracellular calcium completely abolished the kisspeptin-induced calcium elevation. Our results suggest that the major part of the kisspeptin-evoked calcium signal is generated by an action potential-independent calcium influx, possibly through channels of the classical transient receptor potential type, with an additional influx through voltage-gated calcium channels activated by sodium action potentials.
Study Information
pubmed
2010
2010-11-08T00:00:00.000Z
10.1159/000321678
32
42