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Coronary endothelial dysfunction prevented by small-conductance calcium-activated potassium channel activator in mice

Zhiqi Zhang1, Guangbin Shi1, Yuhong Liu1

  • 1Division of Cardiothoracic Surgery, Rhode Island Hospital, Providence, RI.

The Journal of Thoracic and Cardiovascular Surgery
|March 23, 2020
PubMed
Abstract

Insights

A small-conductance calcium-activated potassium (SK) channel activator, NS309, protects coronary microvasculature from cardioplegic-hypoxia and reoxygenation (CP-H/R) injury. However, this protective effect is reduced in diabetic patients and mice.

Area of Science:

  • Cardiovascular Science
  • Endothelial Biology
  • Potassium Channel Function

Background:

  • Coronary microvascular dysfunction is a significant complication following cardiac procedures.
  • Small-conductance calcium-activated potassium (SK) channels play a role in regulating vascular tone and endothelial function.
  • Diabetes mellitus exacerbates cardiovascular injury and impairs endothelial function.

Purpose of the Study:

  • To evaluate the protective effects of an SK channel activator against cardioplegic-hypoxia and reoxygenation (CP-H/R) injury.
  • To compare the efficacy of SK channel activation in diabetic versus nondiabetic subjects.
  • To investigate the impact of CP-H/R on SK channel function and expression in the coronary microvasculature.

Main Methods:

  • Mouse and human coronary endothelial cells and small arteries were isolated.
  • Cells and vessels were subjected to in vitro CP-H/R injury.
  • Treatment with the selective SK channel activator NS309 was administered before and during CP-H/R.
  • SK current density, coronary relaxation, and SK3 channel expression were measured.

Main Results:

  • CP-H/R injury significantly reduced SK current density and coronary relaxation responses.
  • NS309 treatment significantly improved endothelial function recovery after CP-H/R.
  • The protective effect of NS309 was more pronounced in nondiabetic subjects compared to diabetic subjects.
  • Hypoxia led to reduced cell surface SK3 expression and increased cytosolic SK3 expression.

Conclusions:

  • The SK channel activator NS309 demonstrates protective effects on the coronary microvasculature against CP-H/R injury.
  • Diabetic coronary microvasculature exhibits a diminished response to NS309-mediated protection.
  • SK channel dysfunction, including altered expression and localization, may contribute to CP-H/R-induced vascular dysfunction in diabetes.
Keywords:
SK channelscardioplegiacoronary microcirculationdiabetesendothelial functionhypoxiaischemia

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