Vladimir Matchkov

A paradoxical increase of force development in saphenous and tail arteries from heterozygous ANO1 knockout mice

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  • Vladimir V. Matchkov
  • Henrik Black Joergensen
  • ,
  • Dmitrii Kamaev
  • ,
  • Andreas Hoegh Jensen
  • ,
  • Hans Christian Beck, University of Southern Denmark
  • ,
  • Boris V. Skryabin, University of Münster
  • ,
  • Christian Aalkjaer

A Ca2+-activated Cl channel protein, ANO1, is expressed in vascular smooth muscle cells where Cl current is thought to potentiate contraction by contributing to membrane depolarization. However, there is an inconsistency between previous knockout and knockdown studies on ANO1’s role in small arteries. In this study, we assessed cardiovascular function of heterozygous mice with global deletion of exon 7 in the ANO1 gene. We found decreased expression of ANO1 in aorta, saphenous and tail arteries from heterozygous ANO1 knockout mice in comparison with wild type. Accordingly, ANO1 knockdown reduced the Ca2+-activated Cl current in smooth muscle cells. Consistent with conventional hypothesis, the contractility of aorta from ANO1 heterozygous mice was reduced. Surprisingly, we found an enhanced contractility of tail and saphenous arteries from ANO1 heterozygous mice when stimulated with noradrenaline, vasopressin, and K+-induced depolarization. This difference was endothelium-independent. The increased contractility of ANO1 downregulated small arteries was due to increased Ca2+ influx. The expression of L-type Ca2+ channels was not affected but expression of the plasma membrane Ca2+ ATPase 1 and the Piezo1 channel was increased. Expressional analysis of tail arteries further suggested changes of ANO1 knockdown smooth muscle cells toward a pro-contractile phenotype. We did not find any difference between genotypes in blood pressure, heart rate, pressor response, and vasorelaxation in vivo. Our findings in tail and saphenous arteries contrast with the conventional hypothesis and suggest additional roles for ANO1 as a multifunctional protein in the vascular wall that regulates Ca2+ homeostasis and smooth muscle cell phenotype.

Original languageEnglish
Article numbere14645
JournalPhysiological Reports
Number of pages17
Publication statusPublished - Nov 2020

    Research areas

  • ANO1, calcium-activated chloride channel, intracellular calcium, small artery contraction, smooth muscle

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ID: 202020561