Modeling of Membrane Excitability in Gonadotropin-Releasing Hormone-Secreting Hypothalamic Neurons Regulated by Ca²⁺-Mobilizing and Adenylyl Cyclase-Coupled Receptors

Abstract

Gonadotropin-releasing hormone (GnRH) secretion from native and immortalized hypothalamic neurons is regulated by endogenous Ca 2ϩ -mobilizing and adenylyl cyclase (AC)-coupled receptors. Activation of both receptor types leads to an increase in action potential firing frequency and a rise in the intracellular pool mimics the receptor-induced activation of I SOC and I SK , leading to an increase in the firing frequency and Ca 2ϩ influx after a transient cessation of electrical activity. However, increasing the activity of I d simulates the experimental response to forskolin-induced activation of AC. Analysis of the behaviors of I SOC , I d , and I SK in the model reveals the complexity in the interplay of these currents that is necessary to fully account for the experimental results.

Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons

“…I naf represents the fast sodium current; I nap a persistent sodium current; I kdr , I kir , and I km denote delayed rectifier, inward rectifier, and M-type potassium currents, respectively; I cal and I cat are L-and T-type calcium currents, respectively. Equations for these currents are taken from LeBeau et al (2000) and Roberts et al (2009) Conventional Hodgkin-Huxley-type models are used for all currents, as follows:…”

Mechanisms of the Modulation of Pacemaker Activity by GnRH Peptides in the Terminal Nerve-GnRH Neurons

“…In this modulation of membrane excitability, they suggested that the activation of . Furthermore, LeBeau et al (2000) showed the contribution of cAMP-operated inward current to this modulation in GT1 cells. The mechanism of the transient decrease of firing frequency in TN-GnRH neurons (the present study) basically agrees well with these reports.…”

Store-Operated Ca 2+ Influx and Expression of TRPC Genes in Mouse Sinoatrial Node

“…SOCCs have been proposed to provide a pacemaker current in other spontaneously firing cells such as neurons 40 and interstitial cells of Cajal. 41 In embryonic pacemaker cells, before functional pacemaker ionic channels have developed, IP 3 -dependent Ca 2ϩ influx through SOCCs has been described and under these circumstances is thought to contribute to pacemaking.…”