Different pathways with distinct properties conduct dilations in the microcirculation in vivo.
OBJECTIVE
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.


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 K(Ca) channels (charybdotoxin), but dilations to Ado were abolished by the K(ATP) 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 approximately 10 mV in response to ACh, whereas Ado did not alter endothelial membrane potential.


CONCLUSIONS
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.
de Wit
Cor
C
Institut für Physiologie, Universität zu Lübeck, Ratzeburger Allee 160, Lübeck 23538, Germany. dewit@uni-luebeck.de
D000109:Acetylcholine / Q000494:pharmacology*; D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D017630:Connexins / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D015221:Potassium Channels / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein
D000109:Acetylcholine; D000241:Adenosine; D017630:Connexins; D015221:Potassium Channels; D015222:Sodium Channels; D000097003:Gap Junction alpha-5 Protein; D000097006:Gap Junction alpha-4 Protein