Mechanism of action of the epileptogenic drug pentylenetetrazol on a cloned neuronal potassium channel.
The action of the epileptogenic agent pentylenetetrazol (PTZ) on a cloned potassium channel of the rat brain was studied. The Kv1.1 channel was expressed in oocytes of Xenopus laevis and potassium currents were investigated in outside-out and inside-out membrane patches. The results show that PTZ increased the multi-channel potassium currents at strongly negative potentials and decreased them at potentials positive to -35 mV both in outside-out and inside-out membrane patches. The extent and manner of PTZ action, the concentration dependence as well as the onset and time course of the PTZ effect were the same both in outside-out and inside-out membrane patches. The single-channel potassium currents showed an increase in open probability and frequency of opening and a decrease in close time at -50 mV and vice versa at 0 mV with application of PTZ. The amplitude of single-channel current, the open time and the latency to the first channel opening remained almost unchanged under PTZ. The results indicate that PTZ acts via the cell membrane and influences the membrane-associated part of the potassium channel. Thereby, PTZ accelerates the transition from the inactivated to the open state of the channel at strongly negative potentials and reduces it at slightly negative and positive potentials. This mechanism may be the basis for a gate function which is in favour of the development of epileptic discharges.
Madeja
M
M
Institut für Physiologie, Universität Münster, Germany.
Musshoff
U
U
Lorra
C
C
Pongs
O
O
Speckmann
E J
EJ
D000818:Animals; D003001:Cloning, Molecular; D003292:Convulsants / Q000494:pharmacology*; D004553:Electric Conductivity; D005260:Female; D009474:Neurons / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D051381:Rats; D014982:Xenopus laevis
D003292:Convulsants; D015221:Potassium Channels; D010433:Pentylenetetrazole