Evidence that a Ca2+ sparks/STOCs coupling mechanism is responsible for the inhibitory effect of caffeine on electro-mechanical coupling in guinea pig ureteric smooth muscle

L. Borisova, A. Shmygol, Susan Wray, T. Burdyga

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Recent studies have highlighted the role of the sarcoplasmic reticulum (SR) in controlling excitability, Ca2+ signalling and contractility in smooth muscle. Caffeine, an agonist of ryanodine receptors (RyRs) on the SR has been previously shown to effect Ca2+ signalling but its effects on excitability and contractility are not so clear. We have studied the effects of low concentration of caffeine (1 mM) on Ca2+ signalling, action potential and contractility of guinea pig ureteric smooth muscle. Caffeine produced reversible inhibition of the action potentials, Ca2+ transients and phasic contractions evoked by electrical stimulation. It had no effect on the inward Ca2+ current or Ca2+ transient but increased the amplitude and the frequency of spontaneous transient outward currents (STOCs) in voltage clamped ureteric myocytes, suggesting Ca2+-activated K+ channels (BK) are affected by it. In isolated cells and cells in situ caffeine produced an increase in the frequency and the amplitude of Ca2+ sparks as well the number of spark discharging sites per cell. Inhibition of Ca2+ sparks by ryanodine (50 μM) or SR Ca2+-ATPase (SERCA) cyclopiazonic acid (CPA, 20 μM) or BKCa channels by iberiotoxin (200 nM) or TEA (1 mM), fully reversed the inhibitory effect of caffeine on Ca2+ transients and force evoked by electrical field stimulation (EFS). These data suggest that the inhibitory effect of caffeine on the action potential, Ca2+ transients and force in ureteric smooth muscle is caused by activation of Ca2+ sparks/STOCs coupling mechanism.

Original languageEnglish
Pages (from-to)303-311
Number of pages9
JournalCell Calcium
Volume42
Issue number3
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

Keywords

  • Ca sparks
  • Caffeine
  • STOCs
  • Sarcoplasmic reticulum
  • Smooth muscle

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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