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

J Physiol. 2006 Jul 15;574(Pt 2):431-42. doi: 10.1113/jphysiol.2006.110155. Epub 2006 Apr 20.

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 Ca(2+) currents and Ca(2+)-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 Ca(2+) 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 Ca(2+) channels and exhibit an apamin-sensitive I(sAHP), which may allow continuous firing in response to a relatively strong depolarizing input.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Apamin / pharmacology*
  • Calcium / metabolism
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels / drug effects*
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Gene Expression Profiling
  • Gonadotropin-Releasing Hormone / analysis*
  • Neurons / chemistry*
  • Neurons / drug effects
  • Neurons / metabolism*
  • Nickel / pharmacology
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Mutant Strains
  • Small-Conductance Calcium-Activated Potassium Channels / antagonists & inhibitors*
  • Small-Conductance Calcium-Activated Potassium Channels / genetics
  • Small-Conductance Calcium-Activated Potassium Channels / metabolism
  • Spider Venoms / pharmacology
  • omega-Conotoxin GVIA / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels
  • RNA, Messenger
  • SNX 482
  • Small-Conductance Calcium-Activated Potassium Channels
  • Spider Venoms
  • Apamin
  • Gonadotropin-Releasing Hormone
  • Nickel
  • omega-Conotoxin GVIA
  • Nifedipine
  • Calcium