µ-Conotoxins block Kv channels

Leipold, E., F. Ullrich, M. Thiele, A.A. Tietze, H. Terlau, D. Imhof, S.H. Heinemann. Subtype-specific block of voltage-gated K+ channels by µ-conotoxins. Biochemical and Biophysical Research Communications (2017) 482: 1135-1140
Blocking effects of 10 µM µ-SIIIA (blue) and µ-PIIIA (red) on ion currents of the indicated voltage-gated ion channels.

Blocking effects of 10 µM µ-SIIIA (blue) and µ-PIIIA (red) on ion currents of the indicated voltage-gated ion channels.

Illustration: FSU Biophysik

The venoms of marine cone snails contain various types of peptides with neurotoxic activity. The subfamily of µ-conotoxins is known to specifically inhibit the activity of voltage-gated Na+ channels. Because of this feature, µ-conotoxins are interesting lead structures for the development of novel analgesics. However, here we show that PIIIA and SIIIA also block Kv1.2 and Kv1.6 channels, whereas other Kv channels are basically unaffected. This subtype specificity is mediated by the pore structure in the turret domain. µ-conotoxins are therefore less specific than previously assumed.