Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs.
Acid-sensing ion channels (ASICs) extensively exist in both central and peripheral neuronal systems and contribute to many physiological and pathological processes. The protein that interacts with C kinase 1 (PICK1) was cloned as one of the proteins interacting with protein kinase C (PKC) and colocalized with ASIC1 and ASIC2. Here, we used PICK1 knockout (PICK1-KO) C57/BL6 mice together with the whole cell patch clamp, calcium imaging, RT-PCR, Western blot, and immunocytochemistry techniques to explore the possible change in ASICs and the regulatory effects of PKC on ASICs. The results showed that PICK1 played a key role in regulation of ASIC functions. In PICK1-KO mouse cortical neurons, both the amplitude of ASIC currents and elevation of [Ca(2+)](i) mediated by acid were decreased, which were attributable to the decreased expression of ASIC1a and ASIC2a proteins in the plasma membrane. PKC, a partner protein of PICK1, regulated ASIC functions via PICK1. The agonist and antagonist of PKC only altered ASIC currents and acid-induced increase in [Ca(2+)](i) in wild-type, but not in KO mice. In conclusion, our data provided the direct evidence from PICK1-KO mice that a novel target protein, PICK1, would regulate ASIC function and membrane expression in the brain. In addition, PICK1 played the bridge role between PKC and ASICs.
Hu
Zhuang-Li
ZL
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Huang
Chao
C
Fu
Hui
H
Jin
You
Y
Wu
Wen-Ning
WN
Xiong
Qiu-Ju
QJ
Xie
Na
N
Long
Li-Hong
LH
Chen
Jian-Guo
JG
Wang
Fang
F
D062565:Acid Sensing Ion Channels; D000818:Animals; D001921:Brain / Q000201:enzymology / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002540:Cerebral Cortex / Q000201:enzymology / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009474:Neurons / Q000201:enzymology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D015222:Sodium Channels / Q000502:physiology*
C568267:ASIC1 protein, mouse; C568265:ASIC2 protein, mouse; D062565:Acid Sensing Ion Channels; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D015222:Sodium Channels; D011493:Protein Kinase C