Modification of electrophysiological and pharmacological properties of K channels in neuroblastoma cells induced by the oxidant chloramine-T.
The effects of chloramine-T (CL-T) on voltage-dependent potassium channels in neuroblastoma cells were analysed using the whole-cell current recording technique. CL-T irreversibly decreased the peak whole-cell K current, considerably slowed its inactivation and shifted its activation-voltage curve towards positive voltages by 6 mV. Under control conditions, the inactivation of the whole-cell K current could be described by the sum of two exponentials, F and S, whose time constants at +50 mV were tau F = 1.00 +/- 0.15 S and tau S = 5.72 +/- 0.47 S respectively. After CL-T, it could be described by the sum of two (S1 and S2) or three (F, S1 and S2) exponentials whose time constants at +50 mV were: tau F = 0.81 +/- 0.22 S, tau S1 = 6.46 +/- 0.60 S and tau S2 = 48.56 +/- 3.64 S. Under control conditions, F and S inactivating components of the whole-cell K current were blocked by 4-aminopyridine, with a Hill coefficient of 1 and apparent dissociation constants of 0.04 and 0.7 mM respectively. After CL-T, both S1 and S2 components were equally blocked by 4-aminopyridine with a Hill coefficient of 0.25, being reduced to 64% of their control values by 10 mM. CL-T is known to slow the inactivation of sodium channels and to oxidize sulphydryl amino acids and unsaturated lipids. It is concluded that the inactivation gates of voltage-dependent sodium and potassium channels are either constituted of the same amino acid residues or are controlled by unsaturated lipid surrounding or bound to the channel proteins.
Rouzaire-Dubois
B
B
Laboratoire de Physiologie Comparée, URA CNRS 1121, Université Paris-Sud, Orsay, France.
Dubois
J M
JM
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D002700:Chloramines / Q000494:pharmacology*; D004594:Electrophysiology; D005910:Glioma / Q000473:pathology / Q000503:physiopathology / Q000648:ultrastructure; D006822:Hybrid Cells / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009447:Neuroblastoma / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure
D015220:Calcium Channels; D002700:Chloramines; D015221:Potassium Channels; D015761:4-Aminopyridine; D011188:Potassium