D2 dopamine receptors interact directly with N-type calcium channels and regulate channel surface expression levels

被引:47
作者
Kisilevsky, Alexandra E. [1 ]
Zamponi, Gerald W. [1 ]
机构
[1] Univ Calgary, Dept Physiol & Biophys, Hotchkiss Brain Inst, Calgary, AB T2N 4N1, Canada
关键词
dopamine; N-type; G protein; signaling complex;
D O I
10.4161/chan.2.4.6402
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
N-type channels are located on dendrites and at pre-synaptic nerve terminals where they play a fundamental role in neurotransmitter release. They are potently regulated by the activation of a number of different types of pertussis toxin (PTX)-sensitive G alpha(i/o) coupled receptors, which results in voltage-dependent inhibition of channel activity via G beta gamma subunits. Using heterologous expression in HEK 293T cells, we show via whole cell patch clamp recordings that D2 receptors mediate both G beta gamma (i.e., voltage-dependent) and voltage-independent inhibition of channel activity. Furthermore, using co-immunoprecipitation and pull down assays involving the intracellular regions of each protein, we show that D2 receptors and N-type channels form physical signaling complexes. Finally, we use confocal microscopy to demonstrate that D2 receptors regulate N-type channel trafficking to affect the number of calcium channels available at the plasma membrane. Taken together, these data provide evidence for multiple voltage-dependent and voltage-independent mechanisms by which D2 receptor subtypes influence N-type channel activity.
引用
收藏
页码:269 / 277
页数:9
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