Connexin45 (Cx45) cannot replace the function of Cx40 in arterioles

Abstract

Intercellular communication via gap junction channels (GJC) contributes to the coordination of arteriolar tone which is reflected by conducted vasomotor responses. GJC in arterioles are composed of Cx40, 37, 45 and 43. It is unknown if Cx are interchangeable or exhibit specific properties to support cellular function. We investigated if Cx45, which exhibits a smaller conductance than Cx40, can functionally replace Cx40 using mice in which Cx45 is expressed in place of Cx40 (Cx40KI45). Propagation of dilations and constrictions initiated by acetylcholine (ACh, 1mM) or KCl (3M) were studied in arterioles (≈33μm) of the cremaster muscle by intravital microscopy in Cx40-deficient (Cx40KO), Cx40KI45, and wildtype (wt) mice. ACh and KCl were applied with micropipettes in a confined manner. ACh induced a similar dilation in all genotypes at the site of stimulation (58-69%). This dilation was conducted to distant sites and the amplitude was 54±8% at 1200μm upstream in wt. However, in Cx40KO this remote dilation was significantly reduced to 29±4%. In Cx40KI45 remote dilations were impaired to a similar degree (21±4%). In contrast, the propagation of KCl-induced constrictions was comparable in all genotypes (local: −52 to −65%, 600μm:−21 to −25%). In summary, Cx40 function is critical for the conduction of dilations and cannot be compensated for by Cx45 substitution. Therefore, it appears that specific Cx-properties are necessary to support conduction along the endothelium.