Influence of Potassium Channel Blockage on Early Hypoxic Neuronal Excitability

Objective: Potassium channels are ubiquitously expressed in all organisms and constitute the most diverse class of ion channels. Their action is regulated by various factors and is involved in neuronal excitability. 4-aminopyridine (4-AP) is a voltage-sensitive K+ channel inhibitor used in studies of experimental neuronal excitation and in the treatment of demyelinating diseases. It is also known as having a strong convulsant activity on hippocampal slices. We investigated the effect of several K+ channel antagonists on evoked potentials during normoxia and hypoxia. Methods: Field excitatory postsynaptic potentials (fEPSPs), orthodromic (oPSs) and antidromic population spikes (aPSs) were recorded simultaneously in the cornus ammoni1 (CA1) area of rat hippocampal slices. fEPSP/Spike (E-S) ratio was calculated during the experiments to observe sequential changes of pre- and postsynaptic neuronal excitability, especially epileptiform activities. 4-AP, tetraethylammonium (TEA), dequalinium dichloride, paxilline, tertiapin-Q, glibenclamide and barium chloride were tested. Results: Most of the tested K+ channel blockers showed increase of mean amplitudes in oPS, fEPSP and aPS compared to control slices. 4-AP showed most strong increase in oPS (188.5-2.1%). During the early period of hypoxia, epileptiform activities were observed more prominently in 4-AP treated slices, which were not produced in other K+ channel blockers. Those epileptiform activities were accompanied by E-S potentiation (mean 426.6%). Common antiepileptic drugs- valproic acid, phenytoin and carbamazepine- effectively controlled epileptiform activities induced by 4-AP during hypoxia (p=0.0035). Conclusion: Our experimental results thus show that 1) potassium channels significantly increase evoked field potentials, 2 ) epileptiform activities are increased in 4-AP treated slices during hypoxia and they are attributed to E-S potentiation and 3) 4-AP induced epileptiform activities during hypoxia are effectively controlled by antiepileptic drugs. (J Kor Neurotraumatol Soc 2010;6:97-105)