Bay K-8644 in different solvents acts as a transient calcium channel antagonist and a long-lasting calcium channel agonist.
This report describes the effect of Bay K-8644 dissolved in various solvents on two types of calcium channel currents in neuroblastoma cells. Transient calcium channel (T channel) currents were not affected by Bay K-8644 dissolved in ethanol (EtOH) or polyethylene glycol (PEG). However, at the same concentration of 0.6 microM, Bay K-8644 dissolved in dimethylsulfoxide (DMSO) (Bay K-8644/DMSO) decreased the T channel current by 50%. The concentration of all three solvents in the bath was fixed at 0.3% to reach different final concentrations of Bay K-8644. At this fixed solvent concentration, the inhibitory effect of Bay K-8644/DMSO on T channel currents was dose-dependent; the solvents alone did not have any effect on T channel currents; and DMSO pretreatment of cells did not render the T channel current sensitive to Bay K-8644 dissolved in EtOH or PEG. Bay K-8644/DMSO was dried using a flash evaporator and redissolved in EtOH or PEG. Dried Bay K-8644 that was redissolved in EtOH or PEG to achieve a final concentration of 0.6 microM inhibited T channel currents by 39 or 35%, respectively. Furthermore, Bay K-8644 (10 nM) increased L channel currents by 80% with DMSO, but only 30% with EtOH as the solvent. These results show that in neuroblastoma cells Bay K-8644/DMSO, within the concentration range examined, is a T channel antagonist and more effective L channel agonist than Bay K-8644 dissolved in the two other solvents.
Department of Physiology, University of Alberta, Edmonton, Canada.
L
L
Wu
R
R
Wang
E
E
Karpinski
P K
PK
Pang
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000008:administration & dosage / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015221:Potassium Channels; D015222:Sodium Channels; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004121:Dimethyl Sulfoxide