期刊
TOXICON
卷 45, 期 4, 页码 431-442出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.toxicon.2004.11.015
关键词
ion channel gating; potassium channel blockers; potassium channels/drug effects; recombinant fusion proteins; potassium channels; voltage-gated; gating modifier toxins; knottins; KCND
资金
- NHLBI NIH HHS [HL52874] Funding Source: Medline
Kv4 voltage-gated K+ channels are responsible for transient K+ currents in the central nervous system and in the heart. HpTx2 is a peptide toxin that selectively inhibits these currents; making it a useful probe for understanding Kv4 channel structure and drug binding. Therefore, we developed a method to produce large amounts of recombinant HpTx2. Recombinant toxin inhibits all three Kv4 isoforms to the same degree; however, the voltage-dependence of inhibition is less apparent for Kv4.1 than for Kv4.3. Similarly, recombinant HpTx(GS) effects gating characteristics of both channels, but Kv4.1 to a much lesser degree. The toxin lacks affinity for Kv 1.4, Kv2. 1, and Kv3.4. To locate the binding site, the amino acids linking the third and forth membrane spanning segments of Kv4.3 were replaced with analogous amino acids of Kvl.4. The chimeric K+ channel was completely insensitive to block by rHpTx2, Suggesting that its binding site is near the channel's voltage sensor. These data show that rHpTx2(GS) is a gating modifier toxin that binds to a site remote from the pore. (c) 2005 Elsevier Ltd. All rights reserved.
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