Effects of methylmercury on electrical responses of neuroblastoma cells.
The effects of methylmercury on a variety of electrophysiological properties of the N1E-115 neuroblastoma cells were studied using microelectrode and voltage clamp techniques. The action potential was reduced in amplitude with an apparent dissociation constant of the order of 20 microM in the face of relatively small membrane depolarization. Voltage clamp experiments revealed that both peak sodium current and steady-state potassium current were suppressed by 20-60 microM methylmercury, with a stronger effect on the sodium current than on the potassium current. The protein reagents dithiodipyridine and N-ethylmaleimide suppressed both currents. Acetylcholine receptor/channel complexes are vulnerable to the action of methylmercury; the nicotinic fast depolarizing response, the muscarinic hyperpolarizing response, and the muscarinic slow depolarizing response, were all suppressed by 10-30 microM methylmercury. In contrast, the dopamine induced response was not affected by methylmercury at 30 microM. It was concluded that methylmercury impairs both sodium and potassium channel gating mechanisms and suppresses acetylcholine receptor/channel complexes. It remains to be seen whether the effect of chronic exposure is similar to that seen after acute and high level exposure in the present study.
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D004229:Dithiothreitol / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D009447:Neuroblastoma / Q000503:physiopathology; D011950:Receptors, Cholinergic / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects
D007473:Ion Channels; D008767:Methylmercury Compounds; D011950:Receptors, Cholinergic; D011954:Receptors, Dopamine; D000109:Acetylcholine; D005033:Ethylmaleimide; D004229:Dithiothreitol