The modulation of the excitability of primary sensory neurons by Ca²⁺-CaM-CaMKII pathway.
Ca(2+)-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 Ca(2+)-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 Ca(2+)-CaM-CaMKII pathway through modulating VGSCs and VGPCs. Considering the specific distribution of CaMKII and its susceptibility to many analgesic stimuli, Ca(2+)-CaM-CaMKII pathway may play an important role in the peripheral sensory transduction, especially in nociception.
General Surgical Ward Section 2, The First Affiliated Hospital of Henan University of Science and Technology, Henan, China.
Renjie
R
Liang
Xianli
X
Liu
Limin
L
Wei
Wei
W
Wang
Ping
P
Zheng
Xisheng
X
Yan
Yilin
Y
Zhao
Lieju
L
Liu
Xuehong
X
Cao
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D008297:Male; D059225:Nociception; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D012668:Trigeminal Ganglion / Q000378:metabolism
D002147:Calmodulin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2