Direct high affinity modulation of connexin channel activity by cyclic nucleotides

被引:36
作者
Bevans, CG [1 ]
Harris, AL [1 ]
机构
[1] Johns Hopkins Univ, Thomas C Jenkins Dept Biophys, Baltimore, MD 21218 USA
关键词
D O I
10.1074/jbc.274.6.3720
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Connexin channels mediate molecular communication between cells. However, positive identification of biological ligands that directly and noncovalently modulate their activity has been elusive. This study demonstrates a high affinity inhibition of connexin channels by the purine cyclic monophosphates cAMP and cGMP, Purified homomeric connexin-32 and heteromeric connexin-32/connexin-26 channels were inhibited by exposure to nanomolar levels of the nucleotides prior to incorporation into membranes. Access to the site of action, or affinity for the nucleotides, was greatly reduced following incorporation of the connexin channels into membranes, where inhibition required millimolar concentrations of the nucleotides, The high affinity inhibition did not occur with similar concentrations of AMP, ADP, ATP, cTMP, or cCMP. This is the first report of a direct ligand effect on connexin channel function, The high affinity and specificity of the inhibition suggest a biological role in control of connexin channels and also may lead to the application of affinity reagents to study of connexin channel structure-function.
引用
收藏
页码:3720 / 3725
页数:6
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