Integrin-mediated mechanotransduction in renal vascular smooth muscle cells: Activation of calcium sparks

Lavanya Balasubramanian, Abu Ahmed, Chun Min Lo, James S.K. Sham, Kay Pong Yip

Research output: Contribution to journalArticle

Abstract

Integrins are transmembrane heterodimeric proteins that link extracellular matrix (ECM) to cytoskeleton and have been shown to function as mechanotransducers in nonmuscle cells. Synthetic integrin-binding peptide triggers Ca2+ mobilization and contraction in vascular smooth muscle cells (VSMCs) of rat afferent arteriole, indicating that interactions between the ECM and integrins modulate vascular tone. To examine whether integrins transduce extracellular mechanical stress into intracellular Ca2+ signaling events in VSMCs, unidirectional mechanical force was applied to freshly isolated renal VSMCs through paramagnetic beads coated with fibronectin (natural ligand of α5β1-integrin in VSMCs). Pulling of fibronectin-coated beads with an electromagnet triggered Ca 2+ sparks, followed by global Ca2+ mobilization. Paramagnetic beads coated with low-density lipoprotein, whose receptors are not linked to cytoskeleton, were minimally effective in triggering Ca2+ sparks and global Ca2+ mobilization. Preincubation with ryanodine, cytochalasin-D, or colchicine substantially reduced the occurrence of Ca 2+ sparks triggered by fibronectin-coated beads. Binding of VSMCs with antibodies specific to the extracellular domains of γ5-and β1-integrins triggered Ca2+ sparks simulating the effects of fibronectin-coated beads. Preincubation of microperfused afferent arterioles with ryanodine or integrin-specific binding peptide inhibited pressure-induced myogenic constriction. In conclusion, integrins transduce mechanical force into intracellular Ca2+ signaling events in renal VSMCs. Integrin-mediated mechanotransduction is probably involved in myogenic response of afferent arterioles.

Original languageEnglish (US)
Pages (from-to)R1586-R1594
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume293
Issue number4
DOIs
StatePublished - Oct 1 2007

Keywords

  • Fluorescence confocal microscopy
  • Myogenic response
  • Paramagnetic bead

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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