Ca2+-activated K+ channels in the endothelial cell layer involved in modulation of neurogenic contractions in rat penile arteries

Attila Kun, Ana Cristina Martinez, László B. Tankó, János Pataricza, Julius Gy Papp, Ulf Simonsen

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The present study was designed to investigate the functional K+ channels involved in contractions induced by electrical field stimulation in isolated rat penile arteries. Blockers of Ca2+-activated K + channels (KCa), tetraethylammonium, and of large-conductance KCa channels, charybdotoxin and iberiotoxin, as well as a blocker of voltage-dependent K+ channels (KV), 4-aminopyridine, increased resting tension in penile small arteries. In the presence of propranolol and NG-nitro-L-arginine (L-NOARG), electrical field stimulation evoked prazosin-sensitive contractions. In endothelium-intact preparations, these latter contractions were enhanced in the presence of tetraethylammonium and charybdotoxin. However, these blockers did not enhance contractions evoked by exogenously added noradrenaline. Endothelial cell removal increased the neurogenic contractions but tetraethylammonium had no further potentiating effect in these preparations. In the presence of an inhibitor of cyclooxygenase, indomethacin, and inhibitor of nitric oxide (NO) synthase, L-NOARG, acetylcholine evoked relaxations, which were abolished in the presence of either tetraethylammonium or charybdotoxin. In phenylephrine-contracted arteries treated with guanethidine and atropine, electrical field stimulation evoked relaxations, which were partially inhibited by L-NOARG and tetraethylammonium, without any additive effect of these drugs. These observations suggest that both large-conductance KCa channels and KV channels sensitive to iberiotoxin/tetraethylammonium and 4-aminopyridine, respectively, are directly involved in the modulation of myogenic tone of rat penile arteries. Furthermore, activation of endothelial intermediate-conductance KCa channels sensitive to tetraethylammonium and charybdotoxin leads to release of a non-NO nonprostanoid factor, which inhibits release of the neurotransmitter, noradrenaline, but these channels do not appear to be involved in inhibition of contraction evoked by exogenously applied noradrenaline in rat penile arteries.

Original languageEnglish
Pages (from-to)103-115
Number of pages13
JournalEuropean Journal of Pharmacology
Volume474
Issue number1
DOIs
Publication statusPublished - Aug 1 2003

Keywords

  • Electrical field stimulation
  • Endothelium
  • K channel
  • K channel
  • K channel
  • Penile small artery

ASJC Scopus subject areas

  • Pharmacology

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