Inhibitory Effects of 2-Aminoethoxydiphenyl Borate (2-APB) on Three K V 1 Channel Currents

2-Aminoethoxydiphenyl borate (2-APB), a boron-containing compound, is a multitarget compound with potential as a drug precursor and exerts various effects in systems of the human body. Ion channels are among the reported targets of 2-APB. The effects of 2-APB on voltage-gated potassium channels (K )...

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Bibliographic Details
Published inMolecules (Basel, Switzerland) Vol. 28; no. 2
Main Authors Zhao, Wei, Pan, Lanying, Stalin, Antony, Xu, Jianwei, Wu, Liren, Ke, Xianfu, Chen, Yuan
Format Journal Article
LanguageEnglish
Published Switzerland 15.01.2023
Subjects
Animals
Boron Compounds - pharmacology
Humans
Ion Channels
Potassium Channels, Voltage-Gated
KV1.2
KV1.3
KV1.4
potassium channel
2-APB
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Summary:2-Aminoethoxydiphenyl borate (2-APB), a boron-containing compound, is a multitarget compound with potential as a drug precursor and exerts various effects in systems of the human body. Ion channels are among the reported targets of 2-APB. The effects of 2-APB on voltage-gated potassium channels (K ) have been reported, but the types of K channels that 2-APB inhibits and the inhibitory mechanism remain unknown. In this paper, we discovered that 2-APB acted as an inhibitor of three representative human K 1 channels. 2-APB significantly blocked A-type Kv channel K 1.4 in a concentration-dependent manner, with an IC of 67.3 μM, while it inhibited the delayed outward rectifier channels K 1.2 and K 1.3, with IC s of 310.4 μM and 454.9 μM, respectively. Further studies on K 1.4 showed that V549, T551, A553, and L554 at the cavity region and N-terminal played significant roles in 2-APB's effects on the K 1.4 channel. The results also indicated the importance of fast inactivation gating in determining the different effects of 2-APB on three channels. Interestingly, a current facilitation phenomenon by a short prepulse after 2-APB application was discovered for the first time. The docked modeling revealed that 2-APB could form hydrogen bonds with different sites in the cavity region of three channels, and the inhibition constants showed a similar trend to the experimental results. These findings revealed new molecular targets of 2-APB and demonstrated that 2-APB's effects on K 1 channels might be part of the reason for the diverse bioactivities of 2-APB in the human body and in animal models of human disease.
ISSN:1420-3049