Impaired pressure-induced constriction in mouse middle cerebral arteries of ASIC2 knockout mice.
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 beta- and gamma-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.
Gannon
Kimberly P
KP
Dept. of Physiology and Biophysics, Univesity of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Vanlandingham
Lauren G
LG
Jernigan
Nikki L
NL
Grifoni
Samira C
SC
Hamilton
Gina
G
Drummond
Heather A
HA
D062565:Acid Sensing Ion Channels; D000818:Animals; D004305:Dose-Response Relationship, Drug; D053503:Epithelial Sodium Channels / Q000378:metabolism; D005260:Female; D005838:Genotype; D008297:Male; D040542:Mechanotransduction, Cellular; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011312:Pressure; D020033:Protein Isoforms / Q000378:metabolism; D021122:Protein Subunits; D015222:Sodium Channels / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D053503:Epithelial Sodium Channels; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D021122:Protein Subunits; D015222:Sodium Channels; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D011189:Potassium Chloride