Sustained K<SUP>＋</SUP> Outward Currents are Sensitive to Intracellular Heteropodatoxin2 in CA1 Neurons of Organotypic Cultured Hippocampi of Rats

Sustained K<SUP>＋</SUP> Outward Currents are Sensitive to Intracellular Heteropodatoxin2 in CA1 Neurons of Organotypic Cultured Hippocampi of Rats

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 electrophysiologically if heteropodatoxin2 (HpTX₂), 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 HpTX₂ weakly but significantly reduced transient currents. However, when HpTX₂ 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 HpTX₂ effects on Kv4 family. Compared with the effect of cytosolic 4-AP to block transient currents, it is possible that cytosolic HpTX₂ is pharmacologically specific to sustained currents in CA1 neurons. These results suggest that distinctive actions of HpTX₂ inside and outside of neurons are very efficient to selectively reduce specific K⁺ outward currents.