Identification of a mammalian target of κM-conotoxin RIIIK

    loading  Checking for direct PDF access through Ovid

Abstract

Despite the great variability of the conus peptides characterized until now only relatively few have been identified that interact with K+ channels. κM-conotoxin RIIIK (κM-RIIIK) is a 24 amino acid peptide from Conus radiatus, which is structurally similar to μ-conotoxin GIIIA, a peptide known to block specifically skeletal muscle Na+ channels. Recently, it has been shown that κM-RIIIK does not interact with Na+ channels, but inhibits Shaker potassium channels expressed in Xenopus oocytes. It was demonstrated that κM-RIIIK binds to the pore region of Shaker channels and a teleost homologue of the Shaker channel TSha1 was identified as a high affinity target of the toxin. In contrast the mammalian Shaker-homologues Kv1.1, Kv1.3, Kv1.4 are not affected by the toxin. In this study the activity of κM-RIIIK on other mammalian Kv1 K+ channels expressed in Xenopus oocytes was investigated. We demonstrate that κM-conotoxin RIIIK up to 5 μM exhibits no significant effect on Kv1.5 and Kv1.6 mediated currents, but the human Kv1.2 K+ channel is blocked by this peptide. The binding of κM-RIIIK to Kv1.2 channels is state dependent with an IC50 for the closed state of about 200 nM and for the open state of about 400 nM at a test potential of 0 mV. κM-conotoxin RIIIK is the first conotoxin described to block human Kv1.2 potassium channels.

Related Topics

    loading  Loading Related Articles