Cardiovascular Research Advance Access first published online on October 10, 2009
This version [Corrected Proof] published online on October 31, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp340
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Different pathways with distinct properties conduct dilations in the microcirculation in vivo
Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany
* Corresponding author. Tel: +49 451 500 4170, Fax: +49 451 500 4171, Email: dewit{at}uni-luebeck.de
Aims: Conduction of vasomotor signals along the vessel coordinates the behaviour of vascular cells and is attributed to the spread of hyperpolarizations through gap junctions. Intriguingly, conducted dilations encompass larger distances than can be expected by passive electrotonic spread. Because distances are quite distinct for different dilators, we hypothesized that separate pathways with distinct properties are involved.
Methods and results: We characterized local and conducted responses elicited by acetylcholine (ACh) and adenosine (Ado) in the murine microcirculation in vivo. Local (and remote) ACh dilations were nearly abrogated by blockade of KCa channels (charybdotoxin), but dilations to Ado were abolished by the KATP blocker glibenclamide. Bupivacaine, a blocker of Na+ and K+ channels, and similarly the blockade of inwardly rectifying K+ channels (barium) revealed different conduction mechanisms, as the remote dilation to Ado, but not ACh, was abrogated. Surprisingly, expression of connexin37 (Cx37) was not detected in Cx40-deficient arterioles, although abundantly expressed in endothelium of wild-type arterioles. In contrast to the wild-type mice, the amplitude of conducted ACh and Ado dilations decreased similarly with distance in Cx40-deficient mice. Recordings of membrane potential in vivo showed endothelial hyperpolarization by 
10 mV in response to ACh, whereas Ado did not alter endothelial membrane potential.
Conclusion: Distinct pathways conduct responses along the vessel wall which involve dissimilar K+ channels and connexins in initiation and spreading. Most likely, the endothelium is the preferential conduction pathway activated by ACh, whereas in the case of Ado the smooth muscle serves as the signalling pathway. However, in arterioles nearly devoid of Cx40 and Cx37, ACh responses can likewise be conducted along the smooth muscle.
KEYWORDS Ca2+-dependent K+ channels; Conducted responses; Inwardly rectifying K+ channels; Connexin40; Connexin37
Time for primary review: 27 days