The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Sustained $K^+$ Outward Currents are Sensitive to Intracellular Heteropodatoxin2 in CA1 Neurons of Organotypic Cultured Hippocampi of Rats

  • Jung, Sung-Cherl (Department of Physiology, School of Medicine, Jeju National University) ;
  • Eun, Su-Yong (Department of Physiology, School of Medicine, Jeju National University)
  • Received : 2012.07.19
  • Accepted : 2012.10.10
  • Published : 2012.10.30
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Abstract

Blocking or regulating $K^+$ channels is important for investigating neuronal functions in mammalian brains, because voltage-dependent $K^+$ channels (Kv channels) play roles to regulate membrane excitabilities for synaptic and somatic processings in neurons. Although a number of toxins and chemicals are useful to change gating properties of Kv channels, specific effects of each toxin on a particular Kv subunit have not been sufficiently demonstrated in neurons yet. In this study, we tested electro-physiologically if heteropodatoxin2 ($HpTX_2$), known as one of Kv4-specific toxins, might be effective on various $K^+$ outward currents in CA1 neurons of organotypic hippocampal slices of rats. Using a nucleated-patch technique and a pre-pulse protocol in voltage-clamp mode, total $K^+$ outward currents recorded in the soma of CA1 neurons were separated into two components, transient and sustained currents. The extracellular application of $HpTX_2$ weakly but significantly reduced transient currents. However, when $HpTX_2$ was added to internal solution, the significant reduction of amplitudes were observed in sustained currents but not in transient currents. This indicates the non-specificity of $HpTX_2$ effects on Kv4 family. Compared with the effect of cytosolic 4-AP to block transient currents, it is possible that cytosolic $HpTX_2$ is pharmacologically specific to sustained currents in CA1 neurons. These results suggest that distinctive actions of $HpTX_2$ inside and outside of neurons are very efficient to selectively reduce specific $K^+$ outward currents.

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References

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