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The modulation of the excitability of primary sensory neurons by Ca2+–CaM–CaMKII pathway

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Abstract

Ca2+-calmodulin (CaM) dependent protein kinase II (CaMKII) is an important intracellular signal transduction pathway. CaMKII is rich in the primary sensory neurons and specifically presents in the small- and medium-sized neurons. It remains unclear about the modulation on the excitability of primary sensory neurons by Ca2+–CaM–CaMKII pathway. By current clamp recording, we found that the excitability of capsaicin-sensitive small and medium trigeminal ganglion (TG) neurons was significantly reduced by a CaM specific antagonist (W-7) and a CaMKII antagonist (KN-93). The inhibition is represented as the reduction of numbers of action potential (AP), decrease of the amplitude of AP, increase of threshold, and prolongation of duration of AP. Consistently, by voltage clamp recording, we found that both voltage-gated sodium channels (VGSCs) and voltage-gated potassium channels (VGPCs) were inhibited by W-7 and KN-93 in the order of total sodium (Na+) current (INa-T) > sustained potassium (K+) current (IK) > A-type K+ current (IA). In addition, AIP (a selective CaMKII peptide inhibitor) and KN-93 caused a similar inhibition of INa-T and IK. Those evidences show that the excitability of capsaicin sensitive small and medium TG neurons can be regulated by Ca2+–CaM–CaMKII pathway through modulating VGSCs and VGPCs. Considering the specific distribution of CaMKII and its susceptibility to many analgesic stimuli, Ca2+–CaM–CaMKII pathway may play an important role in the peripheral sensory transduction, especially in nociception.

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Acknowledgments

This work was supported by National Institutes of Health (NIH) grant GM-63577, National Natural Science Foundation (NNSF) grant 30571537 and NNSF grant 30271500.

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Correspondence to Lieju Liu or Xuehong Cao.

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Liang, R., Liu, X., Wei, L. et al. The modulation of the excitability of primary sensory neurons by Ca2+–CaM–CaMKII pathway. Neurol Sci 33, 1083–1093 (2012). https://doi.org/10.1007/s10072-011-0907-7

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  • DOI: https://doi.org/10.1007/s10072-011-0907-7

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