Cortical hyperpolarization-activated depolarizing current takes part in the generation of focal paroxysmal activities

被引:65
作者
Timofeev, I [1 ]
Bazhenov, M
Sejnowski, T
Steriade, M
机构
[1] Univ Laval, Fac Med, Neurophysiol Lab, Quebec City, PQ G1K 7P4, Canada
[2] Salk Inst Biol Studies, Howard Hughes Med Inst, Computat Neurobiol Lab, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA
关键词
D O I
10.1073/pnas.132259899
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
During paroxysmal neocortical oscillations, sudden depolarization leading to the next cycle occurs when the majority of cortical neurons are hyperpolarized. Both the Ca2+-dependent K+ currents (I-K(Ca)) and disfacilitation play critical roles in the generation of hyperpolarizing potentials. In vivo experiments and computational models are used here to investigate whether the hyperpolarization-activated depolarizing current (I-h) in cortical neurons also contributes to the generation of paroxysmal onsets. Hyperpolarizing current pulses revealed a depolarizing sag in approximate to20% of cortical neurons. Intracellular recordings from glial cells indirectly indicated an increase in extracellular potassium concentration ([K+](O)) during paroxysmal activities, leading to a positive shift in the reversal potential of K+-mediated currents, including I-h. In the paroxysmal neocortex, approximate to20% of neurons show repolarizing potentials originating from hyperpolarizations associated with depth-electroencephalogram positive waves of spike-wave complexes. The onset of these repolarizing potentials corresponds to maximal [K+](O) as estimated from dual simultaneous impalements from neurons and glial cells. Computational models showed how, after the increased [K+](O), the interplay between I-h, I-K(Ca), and a persistent Na+ current, I-Na(P), could organize paroxysmal oscillations at a frequency of 2-3 Hz.
引用
收藏
页码:9533 / 9537
页数:5
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