Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human glioblastoma multiforme

Sun,Xu; Zhao,Dan; Li,Yong-Li; Sun,Ying; Lei,Xu-Hui; Zhang,Jia-Ning; Wu,Ming-Ming; Li,Rui-Yan; Zhao,Zhe-Feng; Zhang,Zhi-Ren; Jiang,Chuan-Lu

doi:10.3892/or.2013.2777

December 2013 Volume 30 Issue 6

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December 2013 Volume 30 Issue 6

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Article

Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human glioblastoma multiforme

Authors:
- Xu Sun
- Dan Zhao
- Yong-Li Li
- Ying Sun
- Xu-Hui Lei
- Jia-Ning Zhang
- Ming-Ming Wu
- Rui-Yan Li
- Zhe-Feng Zhao
- Zhi-Ren Zhang
- Chuan-Lu Jiang
View Affiliations / Copyright

Affiliations: Department of Neurosurgery, the 2nd Affiliated Hospital, Harbin Medical University, Harbin 150086, P.R. China, Departments of Clinical Pharmacy and Cardiology, the 2nd Affiliated Hospital, Harbin Medical University, Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Harbin 150086, P.R. China
Pages: 2852-2858
|
Published online on: October 2, 2013

https://doi.org/10.3892/or.2013.2777
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Abstract

Recent studies have implicated the acid-sensing ion channel 1 (ASIC1), a proton-gated cation channel that belongs to the epithelial sodium channel (ENaC)/Degenerin family, plays an important role in glioma cell migration. Among the ASIC subunits, only ASIC1a has been found be calcium permeable. However, it has not been determined whether Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates ASIC1 in glioblastoma multiforme (GBM). Herein, we report that ASIC1 and CaMKII assemble to form a functional complex at the plasma membrane of GBM cells. We found that migration ability was significantly attenuated in GBM cells that were pre-treated with autocamtide-2-related inhibitory peptide (AIP), a CaMKII-specific inhibitor, or psalmotoxin 1 (PcTX-1), a selective ASIC1 blocker. Furthermore, the inhibitory effect of AIP or PcTX-1 on migration was diminished when ASIC1 was knocked down in GBM cells; when ASIC1 knockdown GBM cells were concurrently treated with these two inhibitors, cell migration was slightly but significantly decreased. Using whole-cell patch-clamp recordings, we detected an amiloride-sensitive current in GBM cells, and this current was significantly inhibited by both PcTX-1 and AIP. Moreover, the magnitude of this current was dramatically decreased when ASIC1 was knocked down in GBM cells. The addition of AIP failed to further decrease the amplitude of this current. Taken together, these data suggest that ASIC1 and CaMKII form a functional complex in GBM cells. Furthermore, it can be concluded that CaMKII regulates the activity of ASIC1, which is associated with the ability of GBM cells to migrate.

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1	Soroceanu L, Manning TJ Jr and Sontheimer H: Modulation of glioma cell migration and invasion using Cl(−) and K(+) ion channel blockers. J Neurosci. 19:5942–5954. 1999.PubMed/NCBI
2	Kunzelmann K: Ion channels and cancer. J Membr Biol. 205:159–173. 2005. View Article : Google Scholar
3	Roderick HL and Cook SJ: Ca²⁺ signalling checkpoints in cancer: remodelling Ca²⁺ for cancer cell proliferation and survival. Nat Rev Cancer. 8:361–375. 2008.
4	Bubien JK, Keeton DA, Fuller CM, et al: Malignant human gliomas express an amiloride-sensitive Na⁺ conductance. Am J Physiol. 276:C1405–C1410. 1999.PubMed/NCBI
5	Olsen ML, Schade S, Lyons SA, Amaral MD and Sontheimer H: Expression of voltage-gated chloride channels in human glioma cells. J Neurosci. 23:5572–5582. 2003.PubMed/NCBI
6	Weaver AK, Bomben VC and Sontheimer H: Expression and function of calcium-activated potassium channels in human glioma cells. Glia. 54:223–233. 2006. View Article : Google Scholar : PubMed/NCBI
7	Berdiev BK, Xia J, McLean LA, et al: Acid-sensing ion channels in malignant gliomas. J Biol Chem. 278:15023–15034. 2003. View Article : Google Scholar : PubMed/NCBI
8	Kellenberger S and Schild L: Epithelial sodium channel/degenerin family of ion channels: a variety of functions for a shared structure. Physiol Rev. 82:735–767. 2002.PubMed/NCBI
9	Eaton DC and Hamilton KL: The amiloride-blockable sodium channel of epithelial tissue. Ion Channels. 1:251–282. 1988. View Article : Google Scholar : PubMed/NCBI
10	Escoubas P, De Weille JR, Lecoq A, et al: Isolation of a tarantula toxin specific for a class of proton-gated Na⁺ channels. J Biol Chem. 275:25116–25121. 2000. View Article : Google Scholar : PubMed/NCBI
11	Kapoor N, Bartoszewski R, Qadri YJ, et al: Knockdown of ASIC1 and epithelial sodium channel subunits inhibits glioblastoma whole cell current and cell migration. J Biol Chem. 284:24526–24541. 2009. View Article : Google Scholar : PubMed/NCBI
12	Waldmann R and Lazdunski M: H(+)-gated cation channels: neuronal acid sensors in the NaC/DEG family of ion channels. Curr Opin Neurobiol. 8:418–424. 1998.
13	Wemmie JA, Price MP and Welsh MJ: Acid-sensing ion channels: advances, questions and therapeutic opportunities. Trends Neurosci. 29:578–586. 2006. View Article : Google Scholar : PubMed/NCBI
14	Krishtal O: The ASICs: signaling molecules? Modulators Trends Neurosci. 26:477–483. 2003. View Article : Google Scholar : PubMed/NCBI
15	Ettaiche M, Guy N, Hofman P, Lazdunski M and Waldmann R: Acid-sensing ion channel 2 is important for retinal function and protects against light-induced retinal degeneration. J Neurosci. 24:1005–1012. 2004. View Article : Google Scholar : PubMed/NCBI
16	Kapoor N, Lee W, Clark E, et al: Interaction of ASIC1 and ENaC subunits in human glioma cells and rat astrocytes. Am J Physiol Cell Physiol. 300:C1246–C1259. 2011. View Article : Google Scholar : PubMed/NCBI
17	Gao J, Duan B, Wang DG, et al: Coupling between NMDA receptor and acid-sensing ion channel contributes to ischemic neuronal death. Neuron. 48:635–646. 2005. View Article : Google Scholar : PubMed/NCBI
18	Bordey A, Sontheimer H and Trouslard J: Muscarinic activation of BK channels induces membrane oscillations in glioma cells and leads to inhibition of cell migration. J Membr Biol. 176:31–40. 2000. View Article : Google Scholar : PubMed/NCBI
19	Ross SB, Fuller CM, Bubien JK and Benos DJ: Amiloride-sensitive Na⁺ channels contribute to regulatory volume increases in human glioma cells. Am J Physiol Cell Physiol. 293:C1181–C1185. 2007.
20	Rooj AK, McNicholas CM, Bartoszewski R, Bebok Z, Benos DJ and Fuller CM: Glioma-specific cation conductance regulates migration and cell cycle progression. J Biol Chem. 287:4053–4065. 2012. View Article : Google Scholar : PubMed/NCBI
21	Nerbonne JM: Repolarizing cardiac potassium channels: multiple sites and mechanisms for CaMKII-mediated regulation. Heart Rhythm. 8:938–941. 2011. View Article : Google Scholar : PubMed/NCBI
22	Weng XC, Zheng JQ, Li J and Xiao WB: Underlying mechanism of ASIC1a involved in acidosis-induced cytotoxicity in rat C6 glioma cells. Acta Pharmacol Sin. 28:1731–1736. 2007. View Article : Google Scholar : PubMed/NCBI
23	Allen NJ and Attwell D: Modulation of ASIC channels in rat cerebellar Purkinje neurons by ischaemia-related signals. J Physiol. 543:521–529. 2002. View Article : Google Scholar : PubMed/NCBI
24	Xu L, Fukumura D and Jain RK: Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway: mechanism of low pH-induced VEGF. J Biol Chem. 277:11368–11374. 2002. View Article : Google Scholar
25	Ransom CB, O’Neal JT and Sontheimer H: Volume-activated chloride currents contribute to the resting conductance and invasive migration of human glioma cells. J Neurosci. 21:7674–7683. 2001.PubMed/NCBI
26	Cuddapah VA and Sontheimer H: Molecular interaction and functional regulation of ClC-3 by Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) in human malignant glioma. J Biol Chem. 285:11188–11196. 2010. View Article : Google Scholar : PubMed/NCBI
27	Waldmann R: Proton-gated cation channels - neuronal acid sensors in the central and peripheral nervous system. Adv Exp Med Biol. 502:293–304. 2001. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Regulation of ASIC1 by Ca2+/calmodulin-dependent protein kinase II in human glioblastoma multiforme

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