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- W2024406218 endingPage "335" @default.
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- W2024406218 abstract "Our previous work showed that nerve growth factor (NGF) increased the excitability of small-diameter capsaicin-sensitive sensory neurons by activating the p75 neurotrophin receptor and releasing sphingolipid-derived second messengers. Whole cell patch-clamp recordings were used to establish the signaling pathways whereby NGF augments action potential (AP) firing (i.e., sensitization). Inhibition of MEK1/2 (PD-98059), PLC (U-73122, neomycin), or conventional/novel isoforms of PKC (bisindolylmaleimide I) had no effect on the sensitization produced by NGF. Pretreatment with a membrane-permeable, myristoylated pseudosubstrate inhibitor of atypical PKCs (aPKCs: PKMζ, PKCζ, and PKCλ/ι) blocked the NGF-induced increase in AP firing. Inhibitors of phosphatidylinositol 3-kinase (PI3K) also blocked the sensitization produced by NGF. Isolated sensory neurons were also treated with small interfering RNA (siRNA) targeted to PKCζ. Both Western blots and quantitative real-time PCR established that PKMζ, but neither full-length PKCζ nor PKCλ/ι, was significantly reduced after siRNA exposure. Treatment with these labeled siRNA prevented the NGF-induced enhancement of excitability. Furthermore, consistent with the high degree of catalytic homology for aPKCs, internal perfusion with active recombinant PKCζ or PKCι augmented excitability, recapitulating the sensitization produced by NGF. Internal perfusion with recombinant PKCζ suppressed the total potassium current and enhanced the tetrodotoxin-resistant sodium current. Pretreatment with the myristoylated pseudosubstrate inhibitor blocked the increased excitability produced by ceramide or internal perfusion with recombinant PKCζ. These results demonstrate that NGF leads to the activation of PKMζ that ultimately enhances the capacity of small-diameter capsaicin-sensitive sensory neurons to fire APs through a PI3K-dependent signaling cascade." @default.
- W2024406218 created "2016-06-24" @default.
- W2024406218 creator A5041583499 @default.
- W2024406218 creator A5042918141 @default.
- W2024406218 creator A5073607555 @default.
- W2024406218 creator A5085209847 @default.
- W2024406218 creator A5086067249 @default.
- W2024406218 date "2012-01-01" @default.
- W2024406218 modified "2023-10-03" @default.
- W2024406218 title "Nerve growth factor enhances the excitability of rat sensory neurons through activation of the atypical protein kinase C isoform, PKMζ" @default.
- W2024406218 cites W1485657773 @default.
- W2024406218 cites W1493153573 @default.
- W2024406218 cites W1503737214 @default.
- W2024406218 cites W1520176015 @default.
- W2024406218 cites W1529396499 @default.
- W2024406218 cites W1550519555 @default.
- W2024406218 cites W1564302359 @default.
- W2024406218 cites W1596784725 @default.
- W2024406218 cites W1601124709 @default.
- W2024406218 cites W1641731911 @default.
- W2024406218 cites W1677950821 @default.
- W2024406218 cites W1715662620 @default.
- W2024406218 cites W1727356853 @default.
- W2024406218 cites W1754799414 @default.
- W2024406218 cites W1755902553 @default.
- W2024406218 cites W1791013575 @default.
- W2024406218 cites W1817439804 @default.
- W2024406218 cites W1829394502 @default.
- W2024406218 cites W1840804593 @default.
- W2024406218 cites W1956978115 @default.
- W2024406218 cites W1964069732 @default.
- W2024406218 cites W1965779217 @default.
- W2024406218 cites W1966351672 @default.
- W2024406218 cites W1968091649 @default.
- W2024406218 cites W1971459204 @default.
- W2024406218 cites W1971754431 @default.
- W2024406218 cites W1971927237 @default.
- W2024406218 cites W1972297566 @default.
- W2024406218 cites W1973556415 @default.
- W2024406218 cites W1974491267 @default.
- W2024406218 cites W1975995627 @default.
- W2024406218 cites W1976201689 @default.
- W2024406218 cites W1976909984 @default.
- W2024406218 cites W1977795081 @default.
- W2024406218 cites W1977884080 @default.
- W2024406218 cites W1978939719 @default.
- W2024406218 cites W1984448540 @default.
- W2024406218 cites W1988663311 @default.
- W2024406218 cites W1989936643 @default.
- W2024406218 cites W1991342634 @default.
- W2024406218 cites W1993968078 @default.
- W2024406218 cites W1995705528 @default.
- W2024406218 cites W2000403281 @default.
- W2024406218 cites W2001379640 @default.
- W2024406218 cites W2006179472 @default.
- W2024406218 cites W2008083479 @default.
- W2024406218 cites W2009667219 @default.
- W2024406218 cites W2010775795 @default.
- W2024406218 cites W2013947622 @default.
- W2024406218 cites W2015080165 @default.
- W2024406218 cites W2020535122 @default.
- W2024406218 cites W2026332763 @default.
- W2024406218 cites W2027256301 @default.
- W2024406218 cites W2031104034 @default.
- W2024406218 cites W2033781074 @default.
- W2024406218 cites W2035315827 @default.
- W2024406218 cites W2035936653 @default.
- W2024406218 cites W2037347038 @default.
- W2024406218 cites W2044269200 @default.
- W2024406218 cites W2045454837 @default.
- W2024406218 cites W2046525768 @default.
- W2024406218 cites W2049100687 @default.
- W2024406218 cites W2051118171 @default.
- W2024406218 cites W2053802170 @default.
- W2024406218 cites W2057784102 @default.
- W2024406218 cites W2058737281 @default.
- W2024406218 cites W2059028043 @default.
- W2024406218 cites W2062227896 @default.
- W2024406218 cites W2062827290 @default.
- W2024406218 cites W2067385623 @default.
- W2024406218 cites W2068669272 @default.
- W2024406218 cites W2072696125 @default.
- W2024406218 cites W2073338028 @default.
- W2024406218 cites W2085495891 @default.
- W2024406218 cites W2086265159 @default.
- W2024406218 cites W2087695922 @default.
- W2024406218 cites W2088381646 @default.
- W2024406218 cites W2094412568 @default.
- W2024406218 cites W2094441194 @default.
- W2024406218 cites W2097482307 @default.
- W2024406218 cites W2099036181 @default.
- W2024406218 cites W2099173554 @default.
- W2024406218 cites W2100246616 @default.
- W2024406218 cites W2103625610 @default.
- W2024406218 cites W2105493663 @default.
- W2024406218 cites W2108158812 @default.
- W2024406218 cites W2108244474 @default.
- W2024406218 cites W2110852309 @default.