Calcium channel subtypes for cholinergic and nonadrenergic noncholinergic neurotransmission in isolated guinea pig trachea

Chung Hung Shih, Hsin Te Hsu, Kuo Hsien Wang, Chih Hsieh Shih, Wun-Chang Ko

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The Ca 2+ channel subtypes in the neurotransmission of isolated guinea pig trachea were elucidated by monitoring the effects of specific Ca 2+ channel blockers on cholinergic contractions and nonadrenergic noncholinergic (NANC) relaxation elicited by electrical field stimulation (EFS). In isolated guinea pig trachea, cholinergic contractile responses to low- and high-frequency EFS were inhibited by the selective N-type calcium channel blocker, ω-conotoxin MVIIA. ω-Agatoxin IVA (a selective P-type blocker), ω-conotoxin MVIIC (a nonselective N-, Q-, and P-type blocker), and nifedipine (a selective L-type blocker) were ineffective, whereas Ni 2+ (a T- and R-type blocker) facilitated cholinergic contractions and produced a late contracture when its concentration exceeded 30 μM. The more the concentration of Ni 2+ increased, the greater the number of incidences and the late contracture areas which occurred. Late contracture did not seem to be due to the effects of acetylcholine, tachykinins, or other polypeptides, but disappeared in the absence of indomethacin. The NANC relaxant responses elicited by the low- and high-frequency EFS were inhibited by ω-conotoxin MVIIA or Ni 2+, but unaffected by ω-Agatoxin IVA, ω-conotoxin MVIIC, and nifedipine. In the absence of indomethacin, Ni 2+ did not alter the ω-conotoxin MVIIA (100 nM)-resistant component of cholinergic contraction, but significantly further inhibited that of NANC relaxation. These results suggest that in isolated guinea pig trachea, cholinergic contraction is regulated by N-type calcium channels which may mask T- and R-type calcium channels and may be co-modulated by both, while NANC relaxation is mainly and independently controlled by N-, T-, and R-type calcium channels.

Original languageEnglish
Pages (from-to)419-432
Number of pages14
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume382
Issue number5-6
DOIs
Publication statusPublished - Dec 2010

Keywords

  • ω-Agatoxin IVA
  • ω-Conotoxin GVIA
  • ω-Conotoxin MVIIA
  • ω-Conotoxin MVIIC
  • Calcium channels
  • Cholinergic contraction
  • NANC relaxation
  • Nickel
  • Nifedipine

ASJC Scopus subject areas

  • Pharmacology

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