Modification by solvents of the action of nifedipine on calcium channel currents in neuroblastoma cells.
The effect of nifedipine dissolved in different solvents on the two types of calcium channel currents in neuroblastoma cells was investigated using the whole cell version of the patch clamp technique. Nifedipine dissolved in dimethylsulfoxide (nifedipine/DMSO) decreased the transient calcium channel (T channel) current by 50% at a concentration of 10 microM. This inhibitory effect was concentration-dependent and reversible. In contrast, T channel currents were not inhibited by nifedipine at a similar concentration dissolved in acetone or ethanol. Further experiments were carried out with dried nifedipine/DMSO. Dried nifedipine/DMSO powder re-dissolved in acetone or ethanol at a concentration of 10 microM decreased the T channel current by 32% and 37%, respectively. In addition, within the concentration range of 10 nM to 100 microM nifedipine/DMSO inhibited the long-lasting calcium channel (L channel) current more effectively than did nifedipine dissolved in acetone. The concentration of solvent (DMSO, ethanol, acetone) in the bath was fixed at 0.3% to reach different final concentrations of nifedipine. Solvents alone at a final concentration of 0.3% did not show any effect on T or L channel currents. UV absorbance measurements indicated that the combination of nifedipine, solvent and bath solution did not result in precipitation of the dihydropyridine during the experimental protocol. It is concluded that when DMSO is used as the solvent, nifedipine is not only a more effective L channel antagonist but also a T channel antagonist in neuroblastoma cells.
Wu
L
L
Department of Physiology, University of Alberta, Edmonton, Canada.
Karpinski
E
E
Wang
R
R
Pang
P K
PK
D000096:Acetone / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D051379:Mice; D009423:Nervous System Neoplasms / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology*; D012997:Solvents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D012997:Solvents; D000096:Acetone; D000431:Ethanol; D009543:Nifedipine; D004121:Dimethyl Sulfoxide