Potassium currents in epilepsy: effects of the epileptogenic agent pentylenetetrazol on a cloned potassium channel.
The effect of the epileptogenic agent pentylenetetrazol (PTZ) on the cloned rat brain potassium channel Kv1.1 (labelled also RCK1) was investigated in the Xenopus laevis oocyte expression system. The Kv1.1 channel was affected by PTZ in a voltage-dependent manner. PTZ increased the potassium currents at more negative potentials and decreased them at more positive potentials. At a potential of -50 mV the potassium currents were increased by 0.97 and at -20 mV decreased by 0.21 of control value with 100 mmol/l PTZ. The potential at which the inversion from increase to decrease occurred was -33 mV. The inactivation characteristic of the current was shifted to more negative potentials by PTZ. The PTZ effect was obtained at a threshold concentration of 1 mmol/l and increased with rising PTZ concentrations. After removal of the tissues covering the oocyte membrane, the PTZ effect was augmented; with a concentration of 10 mmol/l PTZ the potassium currents at 0 mV were decreased by 0.04 in oocytes with covering tissues and by 0.27 of control value in oocytes without covering tissues. Under current-clamp conditions, PTZ decreased small depolarizations and increased larger depolarizations. This effect of PTZ represents a 'discriminatory function' that may contribute to epileptogenesis in nervous tissues.
Madeja
M
M
Institut für Physiologie, Universität Münster, Germany.
Stocker
M
M
Musshoff
U
U
Pongs
O
O
Speckmann
E J
EJ
D000818:Animals; D003001:Cloning, Molecular; D004594:Electrophysiology; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010433:Pentylenetetrazole / Q000494:pharmacology*; D010957:Plasmids; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014982:Xenopus laevis
D015221:Potassium Channels; D012333:RNA, Messenger; D010433:Pentylenetetrazole