Differential membrane potential and ion current responses to different types of shear stress in vascular endothelial cells

Deborah Lieu, Pamela A. Pappone, Abdul I. Barakat

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Vascular endothelial cells (ECs) distinguish among and respond differently to different types of fluid mechanical shear stress. Elucidating the mechanisms governing this differential responsiveness is the key to understanding why early atherosclerotic lesions localize preferentially in arterial regions exposed to low and/or oscillatory flow. An early and very rapid endothelial response to flow is the activation of flow-sensitive K+ and Cl - channels that respectively hyperpolarize and depolarize the cell membrane and regulate several important endothelial responses to flow. We have used whole cell current- and voltage-clamp techniques to demonstrate that flow-sensitive hyperpolarizing and depolarizing currents respond differently to different types of shear stress in cultured bovine aortic ECs. A steady shear stress level of 10 dyn/cm2 activated both currents leading to rapid membrane hyperpolarization that was subsequently reversed to depolarization. In contrast, a steady shear stress of 1 dyn/cm2 only activated the hyperpolarizing current. A purely oscillatory shear stress of 0 ± 10 dyn/cm2 with an oscillation frequency of either 1 or 0.2 Hz activated the hyperpolarizing current but only minimally the depolarizing current, whereas a 5-Hz oscillation activated neither current. These results demonstrate for the first time that flow-activated ion currents exhibit different sensitivities to shear stress magnitude and oscillation frequency. We propose that flow-sensitive ion channels constitute components of an integrated mechanosensing system that, through the aggregate effect of ion channel activation on cell membrane potential, enables ECs to distinguish among different types of flow.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume286
Issue number6 55-6
DOIs
StatePublished - Jun 2004

Keywords

  • Atherosclerosis
  • Ion channels
  • Mechanotransduction

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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