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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany
FUNCTIONAL CONNEXIN40 PROTEIN IS MANDATORY FOR CONDUCTION OF ENDOTHELIUM-DEPENDENT DILATIONS IN ARTERIOLES AND BLOOD PRESSURE CONTROL
Abstract number: O61
Jobs1 A., Lubkemeier2 I., Willecke2 K., *de Wit1 C.
Background:
Connexin40 (Cx40) is a crucial component in gap junctions (GJ) with a strong impact on function. Cx40-deficient mice exhibit hypertension, renin excess, and impaired conduction of endothelium-dependent dilations. However, Cx37 expression is reduced in these mice which may be due either to hypertension or purely due to the lack of Cx40. A human mutation in Cx40 (Ala96->Ser, A96S) leads to non-conducting gap junctional Cx40 channels allowing to distinguish between these possibilities.
Methods:
We studied conduction of vasomotor signals and blood pressure in mice carrying this mutation homozygously (Cx40A96S) in vivo.
Results:
In arterioles of these mice, mutated Cx40 was identified in endothelial cell membranes. Interestingly, Cx37 was also found in Cx40A96S by immunohistochemistry to a similar amount in endothelial cell membranes as in wildtype. Locally confined arteriolar stimulation by acetylcholine (ACh), bradykinin (Bk), or KCl elicited dilations which spread upstream without decline of the amplitude in wildtype. In contrast, in Cx40A96S the amplitude declined for these dilators with increasing distance significantly. Conducted dilations initiated by adenosine declined similarly in both genotypes. Systolic and diastolic arterial pressure was increased in Cx40A96S (mean pressure by 23 mmHg).
Conclusion:
A functional channel forming Cx40 is required to support conducted dilations and blood pressure regulation, which has been shown previously to be related to Cx40 expression in renin-producing cells. Despite dysfunctional non-conducting Cx40 and hypertension, Cx37 was located in the cell membrane which is, however, not able to sustain Cx40 function. This identifies Cx40 as the leading connexin in terms of functional conductivity.
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 201, Supplement 682 :O61