Differential effects of pulsatile versus steady flow on coronary endothelial membrane potential

Research output: Contribution to journalArticle

Abstract

Steady shear stress stimulates transient hyperpolarization coupled to calcium-sensitive potassium (KCa) channels and sustained depolarization linked to chloride-selective channels. Physiological flow is pulsatile not static, and whereas in vivo data suggest phasic shear stress may preferentially activate KCa channels, its differential effects on both currents remain largely unknown. To determine this interaction, coronary endothelial cells were cultured in glass capillary flow tubes, loaded with the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)trimethine oxonol, and exposed to constant or pulsatile shear stress. The latter was generated by a custom servoperfusion system employing physiological pressure and flow waveforms. Steady shear induced a sustained depolarization inhibited by the Cl- channel blocker DIDS. Even after exposure to steady flow, subsequent transition to pulsatile shear stress further stimulated DIDS-sensitive depolarization. DIDS pretreatment "unmasked" a pulsatile flow-induced hyperpolarization of which magnitude was further enhanced by nifedipine, which augments epoxygenase synthesis. Pulse-shear hyperpolarization was fully blocked by KCa channel inhibition (charybdotoxin + apamin), although these agents had no influence on membrane potential altered by steady flow. Thus KCa-dependent hyperpolarization is preferentially stimulated by pulsatile over steady flow, whereas both can stimulate Cl--dependent depolarizaiion. This supports studies showing greater potency of pulsatile flow for triggering KCa-dependent vasorelaxation.

Original languageEnglish (US)
Pages (from-to)H341-H346
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number1 54-1
StatePublished - Jul 1 2003

Keywords

  • Calcium-sensitive potassium channels
  • Endothelium-derived hyperpolarizing factor
  • Steady shear stress
  • Vasorelaxation

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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