The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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The Downregulation of Somatic A-Type $K^+$ Channels Requires the Activation of Synaptic NMDA Receptors in Young Hippocampal Neurons of Rats

  • Kang, Moon-Seok (Department of Physiology, School of Medicine, Jeju National University) ;
  • Yang, Yoon-Sil (Department of Physiology, School of Medicine, Jeju National University) ;
  • Kim, Seon-Hee (Department of Physiology, School of Medicine, Jeju National University) ;
  • Park, Joo-Min (Department of Physiology, School of Medicine, Jeju National University) ;
  • Eun, Su-Yong (Department of Physiology, School of Medicine, Jeju National University) ;
  • Jung, Sung-Cherl (Department of Physiology, School of Medicine, Jeju National University)
  • Received : 2013.12.05
  • Accepted : 2014.02.26
  • Published : 2014.04.30
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Abstract

The downregulation of A-type $K^+$ channels ($I_A$ channels) accompanying enhanced somatic excitability can mediate epileptogenic conditions in mammalian central nervous system. As $I_A$ channels are dominantly targeted by dendritic and postsynaptic processings during synaptic plasticity, it is presumable that they may act as cellular linkers between synaptic responses and somatic processings under various excitable conditions. In the present study, we electrophysiologically tested if the downregulation of somatic $I_A$ channels was sensitive to synaptic activities in young hippocampal neurons. In primarily cultured hippocampal neurons (DIV 6~9), the peak of $I_A$ recorded by a whole-cell patch was significantly reduced by high KCl or exogenous glutamate treatment to enhance synaptic activities. However, the pretreatment of MK801 to block synaptic NMDA receptors abolished the glutamate-induced reduction of the $I_A$ peak, indicating the necessity of synaptic activation for the reduction of somatic $I_A$. This was again confirmed by glycine treatment, showing a significant reduction of the somatic $I_A$ peak. Additionally, the gating property of $I_A$ channels was also sensitive to the activation of synaptic NMDA receptors, showing the hyperpolarizing shift in inactivation kinetics. These results suggest that synaptic LTP possibly potentiates somatic excitability via downregulating $I_A$ channels in expression and gating kinetics. The consequential changes of somatic excitability following the activity-dependent modulation of synaptic responses may be a series of processings for neuronal functions to determine outputs in memory mechanisms or pathogenic conditions.

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References

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