Inhibition of Ca-channels by diazepam compared with that by nicardipine in pheochromocytoma PC12 cells.
The effects of diazepam on voltage-gated Ca channels were studied in PC12 pheochromocytoma cells using whole-cell voltage-clamp techniques. An inward current activated by a depolarizing voltage step to +10 mV from a holding potential of -60 mV in 10.8 mM Ba was larger than that activated in 10.8 mM Ca. The Ba current was completely blocked by a low concentration of Cd (30 microM) and was also sensitive to nicardipine (100 nM to 10 microM). Diazepam (1-100 microM) inhibited the Ba current in a concentration-dependent manner. Neither diazepam nor nicardipine affected the current-voltage relationship or the dependence on holding potentials of the Ba current. Both slightly accelerated the inactivation time course of the Ba current. When diazepam was applied to the cells in combination with nicardipine, the observed inhibition agreed with a value predicted assuming independent blockade by diazepam and by nicardipine. These results suggest that diazepam inhibits Ca channels in a manner similar to nicardipine, but that the binding sites for diazepam are different from those for nicardipine.
Nakazawa
K
K
Division of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Inoue
K
K
Ohara-Imaizumi
M
M
Fujimori
K
K
Takanaka
A
A
D000818:Animals; D001464:Barium / Q000378:metabolism; D001665:Binding Sites; D015220:Calcium Channels / Q000187:drug effects*; D003975:Diazepam / Q000378:metabolism / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009529:Nicardipine / Q000378:metabolism / Q000494:pharmacology*; D016716:PC12 Cells; D011978:Receptors, Nicotinic / Q000378:metabolism
D015220:Calcium Channels; D007473:Ion Channels; D011978:Receptors, Nicotinic; D001464:Barium; D009529:Nicardipine; D003975:Diazepam