Endothelin-1 and IP3 induced Ca2+ sparks in pulmonary arterial smooth muscle cells

Wei Min Zhang, Mo Jun Lin, James S.K. Sham

Research output: Contribution to journalArticle

Abstract

Endothelin-1 has been implicated as an important modulator or mediator of acute and chronic hypoxic pulmonary hypertension. It has been shown that endothelin-1 increases [Ca2+]i and contraction in pulmonary arterial smooth muscle cells. Recently, we have identified local Ca2+ release transients or Ca2+ sparks, which represent Ca2+ release from clusters of ryanodine receptors on the sarcoplasmic reticulum, in pulmonary arterial smooth muscle cells. These pulmonary Ca 2+ sparks were associated with membrane depolarization, and activated specifically by endothelin-1 via endothelin-A receptor activation of phospholipase C and inositol trisphosphate production, possibly through local Ca2+ signaling between inositol trisphosphate receptors and ryanodine receptors. To test this hypothesis, we measured Ca2+ sparks in intralobar pulmonary arterial smooth muscle cells using laser scanning microscopy, and compared the spatiotemporal properties of Ca2+ sparks activated by endothelin-1 and by photorelease of inositol trisphosphate. We found that both endothelin-1 and inositol trisphosphate had similar effects on Ca2+ sparks. They both increased spark frequency, elevated spark amplitude and prolonged duration, without any significant effect on the spatial spread or size of Ca2+ sparks. These results provide further support to the suggestion that inositol trisphosphate production stimulated by endothelin-1 can account for the activation of Ca2+ sparks in pulmonary arterial smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)S121-S124
JournalJournal of cardiovascular pharmacology
Volume44
Issue numberSUPPL. 1
DOIs
StatePublished - Nov 1 2004

Keywords

  • Ca sparks
  • Caged-inositol trisphosphate (IP)
  • Endothelin-1 (ET-1)
  • Pulmonary arterial smooth muscle cells (PASMCs)

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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