Inward current oscillation underlying tonic contraction caused via ET A receptors in pig detrusor smooth muscle

Shunichi Kajioka, Shinsuke Nakayama, Rachel McCoy, Gordon McMurray, Kihachiro Abe, Alison F. Brading

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Endothelin-1 (ET-1) is a powerful vasoconstricting peptide. Recent studies showed synthesis of ET-1 and the presence of ET receptors in urinary bladder smooth muscle cells. In the present study, we investigated the possible role of ET-1 in detrusor contraction and its underlying mechanisms in terms of electrical activity. ET-1 caused dose-dependent tonic contraction of bladder smooth muscle strips. Whole cell patch-clamp experiments revealed that ET-1 induced a single transient inward current in the majority of detrusor cells and that additional inward current oscillations were induced in one-third of the cells. The inward current oscillation and tonic contraction shared several characteristic features: 1) both activities lasted for a considerable time after ET-1 washout and 2) only prior application of ETA receptor antagonists, not ETB receptor antagonists, significantly suppressed ET-1-induced contractions and the oscillating inward currents. It was concluded that the inward current oscillation underlies ET-1-induced tonic contraction. Experiments with ion substitution and channel blockers suggested that periodic activation of Ca2+-activated C1- channels caused the oscillating inward currents.

Original languageEnglish
Pages (from-to)F77-F85
JournalAmerican Journal of Physiology - Renal Physiology
Volume286
Issue number1 55-1
DOIs
Publication statusPublished - Jan 2004

All Science Journal Classification (ASJC) codes

  • Physiology
  • Urology

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