Effect of cycloheximide on ionic channels in neuroblastoma cell membrane.
The effect of cycloheximide (an inhibitor of protein synthesis) on the ionic currents through sodium and potassium channels was investigated in dialysed voltage-clamped N18 A-1 neuroblastoma cells. The cycloheximide concentration needed for half-inhibition of sodium peak conductance was about 0.5 micrograms/ml for 24 h of incubation. Half-inhibition time of the sodium peak conductance in cells incubated with 15.0 micrograms/ml of cycloheximide was about 9 h. Sodium against potassium ion selectivity, the activation and inactivation parameters were shown to be not affected by cycloheximide. Potassium conductance in similarly treated cells exhibited no consistent changes. The main conclusion is that the decay in peak sodium conductance is caused by diminishing the sodium channel density in the membrane (from 25 to 2.2 channels per micron2). The inhibition effect was evidently mediated by block of protein synthesis and was not the result of direct drug-channel interaction. The half-decay time of sodium peak conductance is interpreted as a possible life-time characteristic of sodium channels in the neuroblastoma cell membrane.
D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002999:Clone Cells; D003513:Cycloheximide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D007473:Ion Channels; D003513:Cycloheximide; D012964:Sodium; D011188:Potassium