Molecular cloning and electrophysiological studies on the first K(+) channel toxin (LmKTx8) derived from scorpion Lychas mucronatus.
LmKTx8, the first toxic gene isolated from the venom of scorpion Lychas mucronatus by constructing cDNA library method, was expressed and characterized physiologically. The mature peptide has 40 residues including six conserved cysteines, and is classified as one of alpha-KTx11 subfamily. Using patch-clamp recording, the recombinant LmKTx8 (rLmKTx8) was used to test the effect on voltage-gated K(+) channels (Kv1.3) stably expressed in COS7 cells and large conductance-Ca(2+)-activated K(+) (BK) channels expressed in HEK293. The results of electrophysiological experiments showed that the rLmKTx8 was a potent inhibitor of Kv1.3 channels with an IC(50)=26.40+/-1.62nM, but 100nM rLmKTx8 did not block the BK currents. LmKTx8 or its analogs might serve as a potential candidate for the development of new drugs for autoimmune diseases.
Wu
Wenlan
W
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, People's Republic of China.
Yin
Shijin
S
Ma
Yibao
Y
Wu
Ying Liang
YL
Zhao
Ruiming
R
Gan
Geliang
G
Ding
Jiuping
J
Cao
Zhijian
Z
Li
Wenxin
W
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004594:Electrophysiology; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000494:pharmacology; D012604:Scorpion Venoms / Q000235:genetics* / Q000494:pharmacology*; D012605:Scorpions / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D017931:DNA Primers; D018076:DNA, Complementary; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D011993:Recombinant Fusion Proteins; D012604:Scorpion Venoms