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Molecular identification of the constitutively‐activated volume‐Regulated Cl‐ channels in hypertrophied ventricular myocytes
Author(s) -
Duan Dayue Darrel,
Wang Guanlei,
Liu Lihui,
Ye Lingyu Linda
Publication year - 2010
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.24.1_supplement.573.6
Subject(s) - myocyte , medicine , endocrinology , tonicity , western blot , chemistry , population , patch clamp , electrophysiology , biochemistry , environmental health , gene
The molecular identity of the constitutively‐activated volume‐regulated Cl − current (VRCC) in hypertrophied cardiac myocytes remains elusive. In this study, ClCn3 −/− mice were used to test whether ClC‐3 encodes the constitutively‐activated VRCCs. Whole‐cell voltage‐clamp and Western blot were used to examine the changes in VRCC and ClC‐3 expression in left ventricular (LV) myocytes from WT and ClCn3 −/− mice subjected to minimally invasive transverse aortic banding (MTAB) for 5 weeks. In most WT MTAB myocytes (76%) a large VRCC was activated under isotonic conditions. Hypotonic cell swelling caused no changes in VRCC while it was significantly inhibited by hypertonic solution. VRCC in WT‐MTAB myocytes had an anion selectivity of I − > Cl − , and was inhibited by tamoxifen, PKC and anti‐ClC‐3 Ab. Expression of ClC‐3 protein in the heart was significantly increased in the WT‐MTAB mice but not in the WT sham‐operated mice. No ClC‐3 expression was detected in the Clcn3 −/− ‐MTAB hearts. In the age‐matched Clcn3 −/− ‐MTAB mice, a significantly smaller VRCC (at +80 mV 2.2±0.5 pA/pF, n=5 vs WT‐MTAB 5.4±0.8 pA/pF, n=5, P<0.01) was present in a significantly smaller population of cells (36%, P<0.05 vs WT‐MATB). But VRCC was not increased by hypotonic stress and was not inhibited by tamoxifen, PKC or anti‐ClC‐3 Ab. Conclusion ClC‐3 may be responsible for the constitutively‐activated VRCCs in hypertrophied heart. (supported by NCRR P‐20 RR‐15581)