Synthetic mammalian C-type natriuretic peptide forms large cation channels

FEBS Lett. 1999 Feb 19;445(1):57-62. doi: 10.1016/s0014-5793(99)00081-2.

Abstract

We report the first evidence that synthetic human C-type natriuretic peptide-22 and the OaC-type natriuretic peptide-39(18-39), a 22 amino acid fragment of the OaC-type natriuretic peptide-39 from platypus venom, can function directly by forming a novel voltage-gated weakly cation-selective channel in negatively charged artificial lipid bilayer membranes. The channel activity is characterized by a tendency for inactivation at negative voltages, e.g. -60 and -70 mV, whereas at positive voltages the channel is fully open. The channel has a maximal cord conductance of 546+/-23 pS (n = 16) and shows weak outward rectification. The sequence and the permeability ratios were P(K)+: P(Cs)+: P(Na)+: P(choline)+ 1:0.88:0.76:0.13, respectively. The addition of 50 mM TEA+ cis (a blocker of outwardly rectifying K+ channels), 20 mM Cs+ cis (a blocker of inwardly rectifying K+ channels) or 0.5 mM glibenclamide cis (a blocker of ATP-sensitive K+ channels) to the cis chamber did not affect the conductance or the kinetics of the OaC-type natriuretic peptide-39(18-39)-formed channels (n = 2-5). It is concluded that the weak cation selectivity, large conductance and high open probability as well as their voltage dependency are consistent with the ability of these peptides to cause that loss of compartmentation of the membrane, which is a characteristic feature of adverse conditions that cause C-type natriuretic peptide-related pathologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Electrophysiology
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Ion Channels / chemical synthesis
  • Ion Channels / physiology*
  • Mammals
  • Molecular Sequence Data
  • Natriuretic Peptide, C-Type / chemical synthesis
  • Natriuretic Peptide, C-Type / physiology*
  • Peptides / chemical synthesis

Substances

  • Intercellular Signaling Peptides and Proteins
  • Ion Channels
  • Peptides
  • ovCNP-39 peptide
  • Natriuretic Peptide, C-Type