| Autor: |
Walter, Helen J., McMahon, Thomas, Dadgar, Jahan, Wang, Dan, Messing, Robert O. |
| Zdroj: |
Journal of Biological Chemistry; August 2000, Vol. 275 Issue: 33 p25717-25722, 6p |
| Abstrakt: |
Chronic exposure to ethanol increases the number of functional L-type voltage-gated calcium channels in neural cells. In PC12 cells, this adaptive response is mediated by protein kinase C δ (PKCδ), but the mechanisms by which this occurs are not known. Since expression of several different calcium channel subunits can increase the abundance of functional L-type channels, we sought to identify which subunits are regulated by ethanol. Incubation of PC12 cells with 120–150 mmethanol for 6 days increased levels of α1C, α2, and β1bsubunit immunoreactivity in cell membranes and selectively increased the abundance of mRNA encoding the α1C-1splice variant of α1C. In cells expressing a fragment of PKCδ (δV1) that selectively inhibits PKCδ, there was no increase in membrane-associated α1C, α2, and β1bimmunoreactivity following chronic ethanol exposure. However, ethanol still increased levels of α1C-1mRNA in these cells. These results indicate that ethanol increases the abundance of L-type channels by at least two mechanisms; one involves increases in mRNA encoding a splice variant of α1Cand the other is post-transcriptional, rate-limiting, and requires PKCδ. |
| Databáze: |
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