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Extracellular acidosis activates ASIC‐like channels in freshly isolated cerebral artery smooth muscle cells
Author(s) -
Chung WenShuo,
Farley Jerry M.,
Drummond Heather A.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1018.13
Subject(s) - acid sensing ion channel , extracellular , acidosis , vascular smooth muscle , biophysics , membrane potential , depolarization , patch clamp , myocyte , chemistry , amiloride , electrophysiology , ion channel , biology , medicine , microbiology and biotechnology , biochemistry , endocrinology , sodium , smooth muscle , receptor , organic chemistry
Our laboratory has shown that certain Acid Sensing Ion Channels (ASIC) mediate pressure‐induced constriction and migration of vascular smooth muscle cells (VSMC). However, electrophysiological evidence of ASIC channels in VSMC is lacking. The purpose of this study was to test the hypothesis that isolated cerebral artery VSMC express ASIC‐like channels. Conventional whole‐cell patch‐clamp technique was used. The criteria of Na + selectivity and gating by extracellular acidosis, features of most ASIC channels, were used to confirm the presence of ASIC‐like channels. We found extracellular acid induced inward currents in 46% of cells tested (n=126, pH 6.5 ‐5.0). At pH = 6.0, the mean amplitude of the current normalized to whole cell capacitance was 7.6±0.9 pA/pF (n=22). While initial and sustained responses to acidosis varied among cells, the ASIC blocker amiloride (100 mM) consistently inhibited the initial response (n = 18, pH 6.0‐6.5). Extracellular acidosis (pH = 6.0) caused depolarization of 7.2±2.4 mV from the resting membrane potential of 25.4±4.1 mV (n = 8) and shifted the whole‐cell reversal potential toward the Nernst potential of Na + (n = 6). Substitution of extracellular Na + by N‐methyl‐d‐glucamine abolished the inward current (n = 8), indicating Na + is the major charge carrier. These findings suggest that functional ASIC‐like currents are present in cerebral VSMCs. Supported by the‐NHLBI.