Altered gating of opiate receptor-modulated K+ channels on amygdala neurons of morphine-dependent rats.

Abstract:

:The molecular mechanism of tolerance to opiate drugs is poorly understood. We have used single-channel patch-clamp recordings to study opiate receptor effects on dissociated neurons from rat amygdala, a limbic region implicated in addiction processes. A 130-pS inwardly rectifying K(+)-preferring cation channel was activated by mu opioid receptors in a membrane-delimited manner. After chronic treatment of the rats with morphine, channel gating changed markedly, with an approximately 100-fold decrease in open probability at a given morphine concentration. The change in channel gating correlated both in time course and in dose of morphine treatment with the development of functional opiate dependence and appeared to arise at a step after G-protein activation and before channel permeation by K(+). This decreased receptor-channel coupling appears to be large enough to account quantitatively for opiate tolerance and may represent one of the mechanisms through which tolerance occurs.

authors

Chen X,Marrero HG,Murphy R,Lin YJ,Freedman JE

doi

10.1073/pnas.97.26.14692

keywords:

subject

Has Abstract

pub_date

2000-12-19 00:00:00

pages

14692-6

issue

26

eissn

0027-8424

issn

1091-6490

pii

97/26/14692

journal_volume

97

pub_type

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