Ca2+/calmodulin-dependent protein kinase II potentiates ATP responses by promoting trafficking of P2X receptors

Guang Yin Xu, Li Yen Mae Huang

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60 Scopus citations


To elucidate the functional link between Ca2+/calmodulin protein kinase II (CaMKII) and P2X receptor activation, we studied the effects of electrical stimulation, such as occurs in injurious conditions, on P2X receptor-mediated ATP responses in primary sensory dorsal root ganglion neurons. We found that endogenously active CaMKII upregulates basal P2X3 receptor activity in dorsal root ganglion neurons. Electrical stimulation causes prolonged increases in ATP currents that lasts up to ≈45 min. In addition, the total and phosphorylated CaMKII are also up-regulated. The enhancement of ATP currents depends on Ca2+ and calmodulin and is completely blocked by the CaMKII inhibitor, 2-[N-(2-hydroxyethyl)]-N-(4-methoxybenzenesulfonyl) lamino-N-(4-chlorocinnamyl)-N-methylbenzylamine). Western analyses indicate that electrical stimulation enhances the expression of P2X3 receptors in the membrane and that the enhancement is blocked by the inhibitor. These results suggest that CaMKII up-regulated by electrical stimulation enhances ATP responses by promoting trafficking of P2X receptors to the membrane and may play a key role in the sensitization of P2X receptors under injurious conditions.

Original languageEnglish (US)
Pages (from-to)11868-11873
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number32
StatePublished - Aug 10 2004

ASJC Scopus subject areas

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