Repository of Research and Investigative Information

Repository of Research and Investigative Information

Baqiyatallah University of Medical Sciences

The blocking activity of different toxins against potassium channels Kv3.4 in RLE cells

(2006) The blocking activity of different toxins against potassium channels Kv3.4 in RLE cells. Iran Biomed J. pp. 169-174. ISSN 1028852X (ISSN)

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Background: K+ channel toxins are essential tools for the first purifications, analysis of subunit structures and brain localization of voltage-gated K+ (Kv) channels. The effects of a lot of toxins on Kv are not fully known. Methods: Using whole-cell patch clamping technique the action of a series of toxins on Kv3.4 current in rat liver cells with expressed Kv3.4 channels (RLE) cloned cells was investigated. The cells were grown in Williams E medium and after 6-8 days, they were suitable for patch clamping. A family of currents was recorded during voltage-clamp steps to various potentials applied from a holding potential of -60 mV to 60-80 mV in 10 mV increments. Results: Upon depolarization, all channels were opened with a sigmoidal time course, reached to the peak within a few 10th of milliseconds and then slowly inactivated. Bath application of tetraethyl ammonium (TEA) or 3, 4-diaminopyridine (DAP) reduced the current dose dependently and inhibited it completely at 3 mM and 25 μM respectively. The Bunodosoma granulifera (BgK) and Heteractis magnifica (HmK) toxins at concentrations up to 30 and 10 μM respectively could not completely inhibit the current. On the hand, toxins such as β-bungarotoxin, corotoxin, novel toxin and dendrotoxins I (DIP) and K (DPK) even in high concentrations (up to 100 mM) had not any significant effect on Kv3.4 current. Comparison of chemical structures of these effective agents with other reported effective toxins such as blood depressing substances (BDS I and II) show no homology between them, but specially the potency of 3, 4-DAP is comparable with these toxins. Conclusion: These results showed that, the Kv3.4 is more sensitive than other K+ channels to 3, 4-DAP. The sensitivity of this channel to the TEA is low (at mM concentration). More investigation is necessary to find more selective and potent inhibitor of Kv3.4 channels.

Item Type: Article
Keywords: 3, 4-Diaminopyridine (DAP) Patch clamping Rat liver cells with expressed Kv3.4 channels (RLE) cells Tetraethyl ammonium (TEA) Voltage-gated K+ (Kv)3.4 channel 3,4 diaminopyridine beta bungarotoxin bunodosoma granulifera toxin derivative corotoxin dendrotoxin dendrotoxin derivative heteractis magnifica toxin derivative sea anemone toxin Shaw potassium channel snake venom tetrylammonium unclassified drug animal cell article cell clone cell growth chemical structure controlled study dose response drug inhibition electrophysiology liver cell nonhuman patch clamp protein expression sequence homology voltage clamp whole cell Bunodosoma granulifera Heteractis magnifica Rattus
Page Range: pp. 169-174
Journal or Publication Title: Iran Biomed J
Journal Index: Scopus
Volume: 10
Number: 4
ISSN: 1028852X (ISSN)
Depositing User: مهندس مهدی شریفی

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