Mechanical stimulation regulates voltage-gated potassium currents in cardiac microvascular endothelial cells

Jinping Fan, Kenneth B. Walsh

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Vascular endothelial cells are constantly exposed to mechanical forces resulting from blood flow and transmural pressure. The goal of this study was to determine whether mechanical stimulation alters the properties of endothelial voltage-gated K+ channels. Cardiac microvascular endothelial cells (CMECs) were isolated from rat ventricular muscle and cultured on thin sheets of silastic membranes. Membrane currents were measured with the use of the whole-cell arrangement of the patch-clamp technique in endothelial cells subjected to static stretch for 24 hours and compared with measurements from control, nonstretched cells. Voltage steps positive to -30 mV resulted in the activation of a time-dependent, delayed rectifier K+ current (I(K)) in the endothelial cells. Mechanically induced increases of 97%, 355%, and 106% at +30 mV were measured in the peak amplitude of I(K) in cells stretched for 24 hours by 5%, 10%, and 15%, respectively. In addition, the half-maximal voltage required for I(K) activation was shifted from +34 mV in the nonstretched cells to -5 mV in the stretched cells. Although I(K) in both groups of CMECs was blocked to a similar extent by tetraethylammonium, currents in the stretched endothelial cells displayed an enhanced sensitivity to inhibition by charybdotoxin. Preincubation of the CMECs with either pertussis toxin or phorbol 12-myristate 13-acetate-during the 24 hours of cell stretch did not prevent the increase in I(K). The application of phorbol 12-myristate 13-acetate and static stretch stimulated the proliferation of CMECs. Stretch-induced regulation of K+ channels may be important to control the resting potential of the endothelium and may contribute to capillary growth during periods of mechanical perturbation.

Original languageEnglish (US)
Pages (from-to)451-457
Number of pages7
JournalCirculation Research
Volume84
Issue number4
DOIs
StatePublished - Mar 5 1999

Keywords

  • Endothelial cell
  • Protein kinase C
  • Stretch
  • Voltage-gated K channel

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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