کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2009846 | 1066690 | 2007 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Mutation of threonine 422 to glutamic acid mimics the phosphorylation state and alters the action of deltamethrin on Cav2.2 Mutation of threonine 422 to glutamic acid mimics the phosphorylation state and alters the action of deltamethrin on Cav2.2](/preview/png/2009846.png)
Effects of deltamethrin on voltage-sensitive calcium channels (VSCC) from rat brain (Cav2.2) expressed in Xenopus oocytes were assessed electrophysiologically. Deltamethrin reduced peak current of wild-type Cav2.2 in a stereospecific and concentration-dependent manner with an EC50 of 1 × 10−9 M. Phosphorylation of threonine 422 enhances voltage-sensitive calcium current, increases the probability that Cav2.2 will open under depolarizing conditions and antagonizes the inhibition of the channel by the betagamma subunit of heterotrimeric G-protein (Gβγ). Site-directed mutagenesis of threonine 422 to glutamic acid (T422E) results in a channel that acts as if it were permanently phosphorylated. Deltamethrin (10−7 M) significantly enhanced peak current via the T422E channel (1.5-fold) compared to the nontreated control and the increase was significantly greater than for either the wild-type (T422) or T422A (permanently unphosphorylated mutant) channels. The effect of deltamethrin on T422E Cav2.2 was stereospecific and concentration-dependent with an EC50 of 9.8 × 10−11 M. Thus, Cav2.2 is modified by deltamethrin but the resulting perturbation is dependent upon the phosphorylation state of threonine 422.
Journal: Pesticide Biochemistry and Physiology - Volume 88, Issue 3, July 2007, Pages 312–320