Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery

A whole-cell voltage- and current-clamp study

B. C. Guan, J. Q. Si, Zhi-Gen Jiang

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background and purpose: Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined. Experimental approach: Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments. Key results: 18β- & 18α-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 μm, respectively. 18βGA (30 μM) resulted in a R in of 2.2 GΩ and C in of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GΩ & 6.1 pF). The GAs (≥30 μM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18βGA also activated a non-selective cation conductance while 18αGA 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 18β- & 18αGA with an IC 50 of 4.3 & 7.8 μM, respectively. Conclusions and Implications: 18βGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at ≥30 μM while causing a mild depolarization by a complex conductance alteration. 18βGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18αGA at 30-100 μM failed to fully block the gap junctions while exerting side actions.

Original languageEnglish (US)
Pages (from-to)1049-1060
Number of pages12
JournalBritish Journal of Pharmacology
Volume151
Issue number7
DOIs
StatePublished - Aug 2007

Fingerprint

Glycyrrhetinic Acid
Gap Junctions
Cochlea
Vascular Smooth Muscle
Smooth Muscle Myocytes
Guinea Pigs
Arteries
Patch-Clamp Techniques
Blood Vessels
Cations
Membranes

Keywords

  • Acetylcholine
  • Arteriole
  • Cochlea
  • EDHF
  • Gap junction
  • Membrane input conductance
  • Vascular

ASJC Scopus subject areas

  • Pharmacology

Cite this

Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery : A whole-cell voltage- and current-clamp study. / Guan, B. C.; Si, J. Q.; Jiang, Zhi-Gen.

In: British Journal of Pharmacology, Vol. 151, No. 7, 08.2007, p. 1049-1060.

Research output: Contribution to journalArticle

@article{125c33855342473daa336fab4a6ba6bd,
title = "Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery: A whole-cell voltage- and current-clamp study",
abstract = "Background and purpose: Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined. Experimental approach: Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments. Key results: 18β- & 18α-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 μm, respectively. 18βGA (30 μM) resulted in a R in of 2.2 GΩ and C in of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GΩ & 6.1 pF). The GAs (≥30 μM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18βGA also activated a non-selective cation conductance while 18αGA 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 18β- & 18αGA with an IC 50 of 4.3 & 7.8 μM, respectively. Conclusions and Implications: 18βGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at ≥30 μM while causing a mild depolarization by a complex conductance alteration. 18βGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18αGA at 30-100 μM failed to fully block the gap junctions while exerting side actions.",
keywords = "Acetylcholine, Arteriole, Cochlea, EDHF, Gap junction, Membrane input conductance, Vascular",
author = "Guan, {B. C.} and Si, {J. Q.} and Zhi-Gen Jiang",
year = "2007",
month = "8",
doi = "10.1038/sj.bjp.0707244",
language = "English (US)",
volume = "151",
pages = "1049--1060",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "7",

}

TY - JOUR

T1 - Blockade of gap junction coupling by glycyrrhetinic acids in guinea pig cochlear artery

T2 - A whole-cell voltage- and current-clamp study

AU - Guan, B. C.

AU - Si, J. Q.

AU - Jiang, Zhi-Gen

PY - 2007/8

Y1 - 2007/8

N2 - Background and purpose: Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined. Experimental approach: Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments. Key results: 18β- & 18α-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 μm, respectively. 18βGA (30 μM) resulted in a R in of 2.2 GΩ and C in of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GΩ & 6.1 pF). The GAs (≥30 μM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18βGA also activated a non-selective cation conductance while 18αGA 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 18β- & 18αGA with an IC 50 of 4.3 & 7.8 μM, respectively. Conclusions and Implications: 18βGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at ≥30 μM while causing a mild depolarization by a complex conductance alteration. 18βGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18αGA at 30-100 μM failed to fully block the gap junctions while exerting side actions.

AB - Background and purpose: Glycyrrhetinic acids (GAs) are widely used as gap junction blockers, but their efficacy and side effects have not been well determined. Experimental approach: Whole-cell electrical recordings were made from vascular smooth muscle cells (VSMCs) embedded in or dissociated from, guinea pig cochlear artery segments. Key results: 18β- & 18α-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 μm, respectively. 18βGA (30 μM) resulted in a R in of 2.2 GΩ and C in of 12 pF, comparable to those of freshly dissociated VSMCs (3.1 GΩ & 6.1 pF). The GAs (≥30 μM) caused a depolarization in VSMCs in situ. In dispersed VSMCs, they both inhibited delayed rectifiers; 18βGA also activated a non-selective cation conductance while 18αGA 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 18β- & 18αGA with an IC 50 of 4.3 & 7.8 μM, respectively. Conclusions and Implications: 18βGA blocked the vascular gap junctions, achieving a complete electrical isolation of the recorded VSMC at ≥30 μM while causing a mild depolarization by a complex conductance alteration. 18βGA suppressed the ACh-induced current in VSMC by blocking the myoendothelial gap junction and by a non-junctional action. 18αGA at 30-100 μM failed to fully block the gap junctions while exerting side actions.

KW - Acetylcholine

KW - Arteriole

KW - Cochlea

KW - EDHF

KW - Gap junction

KW - Membrane input conductance

KW - Vascular

UR - http://www.scopus.com/inward/record.url?scp=34547579274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547579274&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0707244

DO - 10.1038/sj.bjp.0707244

M3 - Article

VL - 151

SP - 1049

EP - 1060

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 7

ER -