Differential inhibition of transient and long-lasting calcium channel currents by benzodiazepines in neuroblastoma cells.
The effects of diazepam, nitrazepam, clonazepam, and Ro5-4864 on transient (type I) and long-lasting (type II) calcium channels associated with low-affinity benzodiazepine receptors were investigated using the whole-cell patch-clamp technique. Clonazepam (100 microM), a specific agonist for the central-type benzodiazepine receptor, reduced transient currents through the type I calcium channel by 40% without affecting long-lasting currents through the type II calcium channel. Diazepam and nitrazepam (100 microM), non-specific agonists for both the central- and peripheral-type benzodiazepine receptors, reduced both transient and long-lasting currents equally by 25-30%. A similar non-selective inhibition was observed by Ro5-4864 (1-10 microM), a specific agonist for the peripheral-type benzodiazepine receptor. It is concluded that the two calcium channel types are regulated differentially by two different kinds of benzodiazepines; central-type for type I channel and peripheral-type for both type I and type II channels.
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
S
S
Watabe
M
M
Yoshii
N
N
Ogata
A
A
Tsunoo
T
T
Narahashi
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity; D004594:Electrophysiology; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D011963:Receptors, GABA-A / Q000502:physiology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D011963:Receptors, GABA-A; D001569:Benzodiazepines