The naphthalenesulphonamide calmodulin antagonist W7 and its 5-iodo-1-C8 analogue inhibit potassium and calcium currents in NG108-15 neuroblastoma x glioma cells in a manner possibly unrelated to their antagonism of calmodulin.
Patch clamp techniques were used to record voltage-sensitive calcium and potassium currents from NG108-15 cells. N-(6-aminohexyl)-5-chloro-1-naphthalene- sulphonamide (W7), a calmodulin (CaM) antagonist and its more potent (10 times) 5-iodo-1-C8 analogue (J8) inhibited these currents in a dose-dependent manner. The inhibition was not dependent on internal or external Ca2+. W7 was about four times more potent as an inhibitor of the transient potassium current (IC50 = 8 microM) than of the M-current or of the calcium current. J8 was also selective for the potassium currents (IC50 values: transient current 4 microM, M-current 11 microM) compared to the calcium current (IC50 36 microM). It is suggested that the inhibition does not result from an anti-CaM action of the compounds.
Caulfield
M P
MP
Department of Pharmacology, University College London, U.K.
Robbins
J
J
Sim
J A
JA
Brown
D A
DA
Mac Neil
S
S
Blackburn
G M
GM
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002460:Cell Line; D005071:Evoked Potentials / Q000187:drug effects; D005910:Glioma; D006822:Hybrid Cells / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013449:Sulfonamides / Q000494:pharmacology*
D015220:Calcium Channels; D002147:Calmodulin; D015221:Potassium Channels; D013449:Sulfonamides; C064991:N-(8-aminohexyl)-5-iodonaphthalene-1-sulfonamide; C017967:W 7