Journal
NEUROLOGICAL SCIENCES
Volume 33, Issue 5, Pages 1083-1093Publisher
SPRINGER-VERLAG ITALIA SRL
DOI: 10.1007/s10072-011-0907-7
Keywords
Ca2+/calmodulin-dependent protein kinase II; Neuron; Voltage-gated sodium channels; Voltage-gated potassium channels; Nociception
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Funding
- National Institutes of Health (NIH) [GM-63577]
- National Natural Science Foundation (NNSF) [30571537, 30271500]
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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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