The SK channel blocker apamin inhibits slow afterhyperpolarization currents in rat gonadotropin-releasing hormone neurones

Gonadotropin-releasing hormone (GnRH) neurones play an essential role in the hypothalamopituitary-gonadal axis. As for other neurones, the discharge pattern of action potentials is important for GnRH neurones to properly function. In the case of a luteinizing hormone (LH) surge, for example, GnRH neurones are likely to continuously fire for more than an hour. For this type of firing, GnRH neurones must have a certain intrinsic property. To address this issue, we investigated the voltage-gated Ca2+ currents and Ca2+-activated voltage-independent K+ currents underlying afterhyperpolarization, because they affect cell excitability. Dispersed GnRH neurones from adult GnRH-EGFP (enhanced green fluorescent protein) transgenic rats were cultured overnight and then used for an electrophysiological experiment involving the perforated patch-clamp configuration. The GnRH neurones showed five subtypes of voltage-gated Ca2+ currents, i.e. the T-, L-, N-, P/Q- and R-types. The GnRH neurones also showed a slow afterhyperpolarization current (I-sAHP), but not a medium one. It is reported that the SK channel blocker apamin (10 pm-100 nm) blocks a medium afterhyperpolarization current but not an I-sAHP. In contrast to previous reports, the IsAHP observed in rat GnRH neurones was potently blocked by apamin. In addition, the GnRH neurones expressed transcripts for SK1-3 channels. The results indicate that rat GnRH neurones express all five subtypes of voltage-gated Ca2+ channels and exhibit an apamin-sensitive I-sAHP, which may allow continuous firing in response to a relatively strong depolarizing input.