Background: 

Pericytes - the interface between parenchymal cells and capillaries - could translate tissue derived activity signals into changes of local blood flow via conducted dilation as elicited by endothelial hyperpolarization. We studied the potential role of gap junctional (GJ) communication between pericytes and endothelial cells in this process.

Methods: 

Pericytes were isolated, selected and characterized from hamster thigh muscle using pericyte markers. Expression of connexins (Cx) and functional GJs were studied by dye spreading and patch clamp; changes in the membrane potential of pericytes and co-cultured HUVEC were investigated using DiBAC4(3) (4mM).

Results: 

All pericytes expressed Cx43 (immunohistochemistry) and dye injection revealed functional GJ between pericytes and co-cultured HUVEC. A subset of the pericytes showed channel activities consistent with Kv1.5 (patch clamp). Pericytes responded to stimulation by flufenamic acid (300 mM) with a significant hyperpolarization (D: -18.8±5.6 arbitrary units (au); n=5) whereas HUVEC alone did not respond (D: 0.4±0.8 au; n=20). However, hyperpolarization was observed in adjacent HUVEC which were co-cultured with pericytes (D: -8.6±3.3 au; n=15). After incubation periods with DiBAC4(3) longer than 30 min neither hyperpolarization, nor dye transfer from Pericytes was observed in HUVEC, suggesting that prolonged exposure to DiBAC4(3) blocked GJ communication.

Conclusion: 

Skeletal muscle pericytes express Cx43 and establish functional GJ with endothelial cells. They are thereby able to transmit a hyperpolarizing signal to the adjacent endothelium. This hyperpolarization could principally induce a conducted dilation as shown before for EDHF mediated dilations. However, microcirculatory studies are necessary to functionally prove this hypothesis in vivo.