ZD 7288 inhibits T-type calcium current in rat hippocampal pyramidal cells.
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.
Sánchez-Alonso
J L
JL
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense, Ciudad Universitaria, 28040 Madrid, Spain.
Halliwell
J V
JV
Colino
A
A
D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000502:physiology*; D002317:Cardiovascular Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009532:Nickel / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D002317:Cardiovascular Agents; D011743:Pyrimidines; D026941:Sodium Channel Blockers; C082246:ICI D2788; D013779:Tetrodotoxin; D009532:Nickel; D009543:Nifedipine