ZD 7288 inhibits T-type calcium current in rat hippocampal pyramidal cells

Neurosci Lett. 2008 Jul 18;439(3):275-80. doi: 10.1016/j.neulet.2008.05.016. Epub 2008 May 10.

Abstract

Many studies have used the channel blocker ZD 7288 to assess possible physiological and pathophysiological roles of hyperpolarization-activated cation currents (Ih). In view of the known interplay between Ih and other membrane conductances, the effects in Wistar rats of ZD 7288 on low-voltage-activated (LVA (- or T-type)) Ca2+ channels were examined in whole-cell patch-clamp recordings from CA1 pyramidal cells in the presence of TTX, TEA, 4-AP, CsCl, BaCl2 and nifedipine. ZD 7288 reduced T-type calcium channel currents and this effect was concentration dependant. ZD 7288 blocked T-type currents when applied extracellularly, but not when included in the recording pipette. Furthermore, ZD 7288 altered the steady-state voltage-dependent inactivation of T-currents. These results indicate that the blocker ZD 7288 has effects on voltage sensitive channels additional to those reported for the Ih current.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, T-Type / physiology*
  • Cardiovascular Agents / pharmacology*
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Electric Stimulation
  • Hippocampus / cytology*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Nickel / pharmacology
  • Nifedipine / pharmacology
  • Patch-Clamp Techniques
  • Pyramidal Cells / drug effects*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Sodium Channel Blockers / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Calcium Channel Blockers
  • Calcium Channels, T-Type
  • Cardiovascular Agents
  • Pyrimidines
  • Sodium Channel Blockers
  • ICI D2788
  • Tetrodotoxin
  • Nickel
  • Nifedipine