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Complex Membrane Actions of Glycyrrhetinic Acid on Vascular Smooth Muscle Cells
Author(s) -
Jiang ZhiGen,
Guan BingCai
Publication year - 2007
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.21.6.a1159
Subject(s) - depolarization , gap junction , biophysics , membrane potential , chemistry , reversal potential , tetraethylammonium , electrophysiology , smooth muscle , anatomy , intracellular , receptor , biology , patch clamp , neuroscience , biochemistry , endocrinology , potassium , organic chemistry
Intercellular electrical and chemical communications mediated by gap junctions play a critical role in development and normal function of many organs including vasculatures and the cochlea. Glycyrrhetinic acid (GA) compounds are widely used gap junction blockers in research but often claimed to have non‐junctional membrane actions, and the latter remain poorly understood. Using whole‐cell recording techniques on smooth muscle cells (SMC) in situ of and acutely dissociated from the spiral modiolar artery (SMA), we analyzed membrane actions of 18βGA. We found that: 18βGA concentration‐dependently increased the input resistance of an in situ SMC from ~200 MΩ up to ~2.2 GΩ, and reduced the capacitive relaxation from multi‐term exponential to single‐term exponential. 30 μM 18βGA induced ~10 mV depolarization and a current that had a negative slope linear I/V relation and a reversal potential ~−37 mV, which was ~2.6 mV more negative than the resting potential of the in situ cells. In dissociated SMCs, 18βGA caused a depolarization of 2.9 ± 0.87 mV (n=15) or an oscillatory inward current of −3.2 ± 0.98 pA (n=18) at −40 mV. The net current induced by 18βGA in 6 of 8 single cells had a linear I/V between −140 and ~−20 mV, a positive slope (106 ± 29 pS, n=6) and an extrapolated reversal potential of −11 ± 6.0 mV (ranged between −24 & 9 mV). Between −20 and +20 mV, the 18βGA‐current I/V showed a largely negative slope sigmoid curve. Step command revealed that this is due to an inhibition of the delayed rectifier K + ‐channel. We conclude that, in addition to gap junction blockade, 18βGA causes opening of a cation conductance and inhibition of a voltage‐gated K + ‐channel. Supported by NIH NIDCD DC 004716 & P30 05983.