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Synergistic actions of diacylglycerol and inositol 1,4,5 trisphosphate for Ca2+-dependent inactivation of TRPC7 channel

  
@article{APS4239,
	author = {Hua Zhang and Ryuji Inoue and Juan Shi and Xiao-hang Jin and Yun-qing Li},
	title = {Synergistic actions of diacylglycerol and inositol 1,4,5 trisphosphate for Ca2+-dependent inactivation of TRPC7 channel},
	journal = {Acta Pharmacologica Sinica},
	volume = {29},
	number = {1},
	year = {2016},
	keywords = {},
	abstract = {Aim: The aim of the present study was to explore the mechanism for the Ca2+-dependent inactivation of the canonical transient receptor potential (TRPC) 7 channel expressed in human embryonic kidney 293 cells. 
Method: The whole-cell patch-clamp technique was used in the study. 
Results: With Ca2+-free external solution, the perfusion of 100 μmol/L carbachol to, or dialysis of the cell with 100 μmol/L guanosine 5'-3-O-(thio)triphosphate (GTPgS), induced large inward currents, respectively. These currents were rapidly inhibited by the addition of 1 mmol/L Ca2+ into the bath, and recovery from this inhibition was only partial after the Ca2+ removal, unless vigorous intracellular Ca2+ buffering with 10 mmol/L 1,2 bis (2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid (BAPTA) (plus 4 mmol/L Ca2+) was employed. In contrast, the current induced by a membrane-permeable analog of diacylglycerol (DAG), 1-oleoyl-2-acetyl-sn-glycerol (OAG; 100 μmol/L) did not undergo the inhibition persisting after Ca2+ removal. Interestingly, the inclusion of inositol 1,4,5 trisphosphate (IP3; 100 μmol/L) in the patch pipette rendered the OAG-induced current susceptible to the persistent Ca2+-mediated inhibition independent of the IP3 receptor in the majority of the tested cells, as evidenced by the inability of heparin and thapsigargin in reversing the effect of IP3. 
Conclusion: The present results suggest that Ca2+ entry via the activated TRPC7 channel plays a critical role in inactivating the channel where the cooperative actions of DAG and IP3 are essentially involved.},
	issn = {1745-7254},	url = {http://www.chinaphar.com/article/view/4239}
}