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- Title
Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery: a whole-cell voltage- and current-clamp study.
- Authors
Guan, B.-C.; Si, J.-Q.; Jiang, Z.-G.
- Abstract
<bold>Background and Purpose: </bold>Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined.<bold>Experimental Approach: </bold>Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments.<bold>Key Results: </bold>18beta- & 18alpha-GA concentration-dependently increased membrane input resistance (R(in)) of in situ VSMCs, with a maximal input conductance (G(in)=1/R(in)) reduction of 92% & 77% and IC(50) of 2.0 & 4.4 microm, respectively. 18betaGA (30 microM) resulted in a R(in) of 2.2 GOmega and C(in) of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GOmega & 6.1 pF). The GAs (> or =30 microM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18betaGA also activated a non-selective cation conductance while 18alphaGA inactivated a voltage-independent K+-conductance. ACh induced an outward current in VSMCs in situ at -40 mV, with a positive slope I/V relation and a reversal potential near E(K). The ACh-induced current was attenuated by 18beta- & 18alphaGA with an IC(50) of 4.3 & 7.8 microM, respectively.<bold>Conclusions and Implications: </bold>18betaGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at > or =30 microM while causing a mild depolarization by a complex conductance alteration. 18betaGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18alphaGA at 30-100 microM failed to fully block the gap junctions while exerting side actions.
- Subjects
GAP junctions (Cell biology); ACETYLCHOLINE; VASCULAR smooth muscle; HOMEOSTASIS; GUINEA pigs as laboratory animals; ANIMAL models in research; ARTERIAL physiology; POTASSIUM metabolism; SMOOTH muscle physiology; AMINOPYRIDINES; ANIMAL experimentation; ARTERIES; BIOLOGICAL transport; CELL membranes; COCHLEA; CYTOLOGICAL techniques; DOSE-effect relationship in pharmacology; ELECTROPHYSIOLOGY; GUINEA pigs; HYDROCARBONS; MEMBRANE proteins; POTASSIUM; RESEARCH funding; SMOOTH muscle; TIME; QUATERNARY ammonium compounds; PHARMACODYNAMICS; PHYSIOLOGY
- Publication
British Journal of Pharmacology, 2007, Vol 151, Issue 7, p1049
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0707244