The role of cardiac capillary endothelial cells in electro-metabolic signaling and blood flow regulation.

Abstract

The “Electro-metabolic signaling (EMS)” hypothesis of blood flow control postulates that ventricular myocytes themselves are simultaneously the end-stage metabolic consumers, sensors and master controllers of their own blood flow. EMS has been studied primarily with an intact perfused mouse papillary muscle preparation (Z-prep). Using the Z-prep, when KATP channels (the metabolic sensors) in ventricular myocytes are activated pharmacologically, cardiac ventricular myocytes produce a time-averaged hyperpolarization that spreads through the electrically coupled capillary endothelial cells (cECs) through the vascular tree. The cECs hyperpolarize the pericytes and the vascular smooth muscle cells which relax as a result of their hyperpolarization and thereby vasodilate to increase blood flow to the downstream ventricular myocytes. To investigate how the cECs contribute directly to the electrical signaling, freshly isolated cECs were prepared and shown to have a resting potential of ∼−35 mV in physiological saline solutions, similar to the reported resting potential in the brain cECs. However, unlike those found in brain cECs and long-term cultured human cardiac microvascular endothelial cells, Ba2+-sensitive inward rectifier K+ currents (Kir) were rarely detected in freshly isolated mouse cardiac cECs. Consistent with our previous report, glibenclamide-sensitive KATP currents in cECs were not generally detected. We thus conclude that EMS is driven by the needs of the ventricular myocytes and that Kir channels in cardiac vasculature play little or no role in regulating EMS in heart.