DIVERSITY OF POTASSIUM CHANNELS CONTRIBUTING TO DIFFERENCES IN BRAIN AREA-SPECIFIC SEIZURE SUSCEPTIBILITY - SENSITIVITY OF DIFFERENT POTASSIUM CHANNELS TO THE EPILEPTOGENIC AGENT PENTYLENETETRAZOL

The effect of the epileptogenic agent pentylenetetrazol on eight clone d voltage-operated mammalian potassium channels (expressed in oocytes of Xenopus laevis) was investigated in order to contribute to an expla nation for the brain area-specific differences in seizure susceptibili ty. Pentylenetetrazol increased the potassium currents at more negativ e and decreased them at more positive potentials for the channels of t he Kv1 gene family, whereas for the other channels the currents were d ecreased over the whole potential range. The sensitivities of the diff erent potassium channels to the epileptogenic agent were different. At a potential of 0 mV, for example, there were strong reductions for th e Kv1.1, Kv1.4 and Kv2.1 currents, whereas the decrease was smaller fo r the Kv1.3 and Kv1.6 currents and was negligible for the Kv1.2, Kv1.5 and Kv3.4 currents. Correlating these data with the distribution patt erns of the potassium channels in the hippocampus, the neocortex and t he cerebellum (representing examples of brain areas of distinct seizur e susceptibility) revealed that in brain areas with higher seizure sus ceptibility the overall sensitivity of the potassium channels to the e pileptogenic agent is augmented. As a whole, the findings give the fir st evidence that the differences in distributions and properties of po tassium channels contribute to differences in the seizure susceptibili ty of brain areas.