Molecular characterization of T-type Ca(2+) channels responsible for low threshold spikes in hypothalamic paraventricular nucleus neurons

Neuroscience. 2008 Sep 9;155(4):1195-203. doi: 10.1016/j.neuroscience.2008.06.055. Epub 2008 Jul 3.

Abstract

The hypothalamic paraventricular nucleus (PVN) is composed of functionally heterogeneous cell groups, possessing distinct electrophysiological properties depending on their functional roles. Previously, T-type Ca(2+) dependent low-threshold spikes (LTS) have been demonstrated in various PVN neuronal types, including preautonomic cells. However, the molecular composition and functional properties of the underlying T-type Ca(2+) channels have not been characterized. In the present study, we combined single cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry and patch-clamp recordings to identify subtypes of T-type Ca(2+) channels expressed in PVN cells displaying LTS (PVN-LTS), including identified preautonomic neurons. LTS appeared at the end of hyperpolarizing pulses either as long-lasting plateaus or as short-lasting depolarizing humps. LTS were mediated by rapidly activating and inactivating T-type Ca(2+) currents and were blocked by Ni(2+). Single cell RT-PCR and immunohistochemical studies revealed Cav3.1 (voltage-gated Ca(2+) channel) as the main channel subunit detected in PVN-LTS neurons. In conclusion, these data indicate that Cav3.1 is the major subtype of T-type Ca(2+) channel subunit that mediates T-type Ca(2+) dependent LTS in PVN neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology*
  • Animals
  • Brain Mapping
  • Calcium Channels, T-Type / classification
  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / metabolism*
  • Cholera Toxin / metabolism
  • Drug Interactions
  • Electric Stimulation / methods
  • In Vitro Techniques
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Neurons / radiation effects
  • Nickel / pharmacology
  • Paraventricular Hypothalamic Nucleus / cytology*
  • Patch-Clamp Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Calcium Channels, T-Type
  • Sodium Channel Blockers
  • Tetrodotoxin
  • Nickel
  • Cholera Toxin