High K+-induced contraction requires depolarization-induced Ca2+ release from internal stores in rat gut smooth muscle

Timo Kirschstein, Mirko Rehberg, Rika Bajorat, Tursonjan Tokay, Katrin Porath, Rüdiger Köhling

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Aim: Depolarization-induced contraction of smooth muscle is thought to be mediated by Ca2+ influx through voltage-gated L-type Ca2+ channels. We describe a novel contraction mechanism that is independent of Ca2+ entry. Methods: Pharmacological experiments were carried out on isolated rat gut longitudinal smooth muscle preparations, measuring isometric contraction strength upon high K+-induced depolarization. Results: Treatment with verapamil, which presumably leads to a conformational change in the channel, completely abolished K+-induced contraction, while residual contraction still occurred when Ca2+ entry was blocked with Cd2+. These results were further confirmed by measuring intracellular Ca2+ transients using Fura-2. Co-application of Cd2+ and the ryanodine receptor blocker DHBP further reduced contraction, albeit incompletely. Additional blockage of either phospholipase C (U 73122) or inositol 1,4,5-trisphophate (IP3) receptors (2-APB) abolished most contractions, while sole application of these blockers and Cd2+ (without parallel ryanodine receptor manipulation) also resulted in incomplete contraction block. Conclusion: We conclude that there are parallel mechanisms of depolarization-induced smooth muscle contraction via (a) Ca2+ entry and (b) Ca2+ entry-independent, depolarization-induced Ca 2+-release through ryanodine receptors and IP3, with the latter being dependent on phospholipase C activation.

Original languageEnglish
Pages (from-to)1123-1131
Number of pages9
JournalActa Pharmacologica Sinica
Volume30
Issue number8
DOIs
Publication statusPublished - Aug 2009

Keywords

  • Calcium channels L-type
  • Inositol phosphates
  • Phospholipase C
  • Ryanodine receptor

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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