Voltage-gated calcium channel activity of gonadotropin-releasing hormone (GnRH) neurons is altered by age and by prenatal androgen exposure in female mice.

Polyendocrine metabolic ovarian syndrome (PMOS), a common cause of infertility, is marked by persistently high luteinizing hormone (LH) pulse frequency, presumably driven by high-frequency GnRH pulses. Prenatally androgenized (PNA) mice mimic neuroendocrine PMOS symptoms including high LH-pulse frequency. GnRH neurons from adult PNA mice have a higher spontaneous firing rate than those from vehicle (VEH) mice; this is reversed in peripubertal mice despite more excitatory inputs at both ages. We hypothesized voltage-gated Ca2+ currents (ICa) help set intrinsic excitability of GnRH neurons and are altered by development and/or PNA treatment. Whole-cell patch-clamp measurements were made of GnRH neuron ICa and excitability in 3 week-old and adult VEH and PNA mice. PNA treatment increased ICa density and depolarized the ICa-half-inactivation potential at both ages. In adults, the half-activation potential of the Ca2+ conductance was depolarized, and the half-inactivation time of the fast ICa component was increased regardless of PNA treatment. There was an age-related change in firing response to current injections driven primarily by more firing in 3 week-old VEH mice; 3 week-old PNA mice had adult-like responses. Blocking small-conductance Ca2+-activated K+ current with apamin increased GnRH neuron firing rate except in adult PNA mice. Apamin changed the post-spike-train membrane response from hyperpolarization to depolarization; during development, this net effect of apamin was smaller in PNA mice. In summary, GnRH neurons from PNA mice have increased ICa and altered ICa kinetics. Ca2+-activated K+ currents are less prominent in GnRH neurons from adult PNA mice, perhaps contributing to their increased spontaneous firing activity.