DETERMINANTS OF PKC-DEPENDENT MODULATION OF A FAMILY OF NEURONAL CALCIUM CHANNELS

被引:183
作者
STEA, A
SOONG, TW
SNUTCH, TP
机构
[1] Biotechnology Laboratory Department, Neuroscience Department, Zoology University of British Columbia, Vancouver
基金
英国医学研究理事会;
关键词
D O I
10.1016/0896-6273(95)90183-3
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The modulation of Ca2+ channel activity by protein kinases contributes to the dynamic regulation of neuronal physiology. Using the transient expression of a family of neuronal Ca2+ channels, we have identified several factors that contribute to the PKC-dependent modulation of Ca2+ channels. First, the nature of the Ca2+ channel alpha(1) subunit protein is critical. Both alpha(1B) and alpha(1E) channels exhibit a 30%-40% increase in peak currents after exposure to phorbol esters, whereas neither alpha(1A) nor alpha(1C) channels are significantly affected. This up-regulation can be mimicked for alpha(1E) channels by stimulation of a coexpressed metabotropic glutamate receptor (type 1 alpha) through a PKC-dependent pathway. Second, PKC-stimulated up-regulation is dependent upon coexpression with a Ca2+ channel beta subunit. Third, substitution of the cytoplasmic domain I-II linker from alpha(1B) confers PKC sensitivity to alpha(1A) channels. The results provide direct evidence for the modulation of a subset of neuronal Ca2+ channels by PKC and implicate alpha(1) and beta subunit interactions in regulating channel activity via second messenger pathways.
引用
收藏
页码:929 / 940
页数:12
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