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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/H1793    most recent 01380.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Gannon, K. P. Articles by Drummond, H. A. PubMed PubMed Citation Articles by Gannon, K. P. Articles by Drummond, H. A.

Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice

¹Department of Physiology and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi; and ²Department of Cellular Biology and Physiology, University of New Mexico Health Science Center, Albuquerque, New Mexico

Submitted 29 November 2007 ; accepted in final form 6 February 2008

Recent studies from our laboratory demonstrated the importance of mechanosensitive epithelial Na⁺ channel (ENaC) proteins in pressure-induced constriction in renal and cerebral arteries. ENaC proteins are closely related to acid-sensing ion channel 2 (ASIC2), a protein known to be required for normal mechanotransduction in certain sensory neurons. However, the role of the ASIC2 protein in pressure-induced constriction has never been addressed. The goal of the current study was to investigate the role of ASIC2 proteins in pressure-induced, or myogenic, constriction in the mouse middle cerebral arteries (MCAs) from ASIC2 wild-type (+/+), heterozygous (+/–), and null (–/–) mice. Constrictor responses to KCl (20–80 mM) and phenylephrine (10^–7–10^–4 M) were not different among groups. However, vasoconstrictor responses to increases in intraluminal pressure (15–90 mmHg) were impaired in MCAs from ASIC2^–/– and ^+/– mice. At 60 and 90 mmHg, MCAs from ASIC2^+/+ mice generated 13.7 ± 2.1% and 15.8 ± 2.0% tone and ASIC2^–/– mice generated 7.4 ± 2.8% and 12.5 ± 2.4% tone, respectively. Surprisingly, MCAs from ASIC2^+/– mice generated 1.2 ± 2.2% and 3.9 ± 1.8% tone at 60 and 90 mmHg. The reason underlying the total loss of myogenic tone in the ASIC2^+/– is not clear, although the loss of mechanosensitive β- and -ENaC proteins may be a contributing factor. These results demonstrate that normal ASIC2 expression is required for normal pressure-induced constriction in the MCA. Furthermore, ASIC2 may be involved in establishing the basal level of myogenic tone.

mechanotransduction; myogenic constriction; degenerin; acid-sensing ion channel