Suppression of maxi-K channel and membrane depolarization by synthetic polycations in single tracheal myocytes

Takako Oshiro, Tsukasa Sasaki, Masayuki Nara, Tsutomu Tamada, Sanae Shimura, Yoshio Maruyama, Kunio Shirato

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Polycationic proteins, e.g., major basic protein from eosinophils or cathepsin G from neutrophils, have been shown to increase nonspecific airway responsiveness. Along with several indirect manners of action, polycations were reported to contract smooth-muscle strips and to raise the cellular Ca2+ concentration as a direct action on airway smooth muscle. However, the mechanistic basis for the direct behavior remains to be elucidated. To address this issues, we examined the effects of synthetic cationic polypeptides poly-L-arginine and poly-L-lysine on fresh single smooth-muscle cells from bovine trachea using a patch-clamp technique. Both of the polycations significantly depolarized the membrane from a baseline of about -40 to -20 mV in a dose-dependent manner. The polycations also suppressed whole-cell spontaneous transient outward current as well as both the conductance (from a baseline of about 130 to 70 pS) and open-state probability (about 25% of control values) of large-conductance Ca2+-dependent K+ channel (maxi-K channel) on excised outside-out patch membranes. The polycations were without effect on the whole-cell Ca2+ currents induced by depolarizing voltage pulses. We concluded that the synthetic polycations had at least two sites of action; one is the delayed rectifier K+ channel that is responsible for the membrane depolarization that increases Ca2+ influx, and the other is the maxi-K channel the suppression of which inhibits muscle relaxation. These results may explain the direct contractile action and, therefore, one of the mechanisms underlying the airway hyperresponsiveness induced by various polycationic proteins.

Original languageEnglish
Pages (from-to)528-534
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume22
Issue number5
DOIs
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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