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

Abstract

Gonadotropin‐releasing hormone (GnRH) neurones play an essential role in the hypothalamo‐pituitary‐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 I_sAHP 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.