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© The Rockefeller University Press, 0022-1295/1998//555/ $5.00
Journal of General Physiology, Volume 111, Number 4, 1998

Article

Specific Antibodies to the External Vestibule of Voltage-gated Potassium Channels Block Current

Ben-Yuan Zhou, Wei Ma, and Xin-Yun Huang

From the Department of Physiology, Cornell University Medical College, New York 10021

Using delayed-rectifier potassium channels as examples, we have designed two specific blockers by generating specific antipeptide antibodies to epitopes in the external vestibules of two channel proteins, Kv1.2 and Kv3.1. These antibodies reduced whole-cell Kv1.2 or Kv3.1 currents in transfected cells and the effect was blocked by the corresponding peptide antigen, but not by control peptides. A control antibody had little effect on Kv1.2 currents and the Kv1.2 blocker antibody had limited effect on other related potassium currents. Furthermore, the Kv1.2 blocking antibody inhibited dendrotoxin binding to Kv1.2 channel proteins in transfected cells. Moreover, using the Kv1.2 blocker antibody, we determined the presence and relative contribution of endogenous Kv1.2 to the overall endogenous K+ currents in NG108 neuronal cells. This guided design of specific channel blockers will facilitate future physiological studies on ion channel functions.

Key Words: ion channels • antibody • inhibitor • neurotoxin

Address correspondence to Xin-Yun Huang, Department of Physiology, Cornell University Medical College, 1300 York Ave., New York, NY 10021. Fax: 212-746-8690; E-mail: xyhuang{at}mail.med.cornell.edu


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