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

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 micromol/L carbachol to, or dialysis of the cell with 100 micromol/L guanosine 5'-3-O-(thio)triphosphate (GTPgammaS), 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,No,No-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 micromol/L) did not undergo the inhibition persisting after Ca2+ removal. Interestingly, the inclusion of inositol 1,4,5 trisphosphate (IP3; 100 micromol/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.

journal_name

Acta Pharmacol Sin

journal_title

Acta pharmacologica Sinica

authors

Zhang H,Inoue R,Shi J,Jin XH,Li YQ

doi

10.1111/j.1745-7254.2008.00721.x

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

90-7

issue

1

eissn

1671-4083

issn

1745-7254

journal_volume

29

pub_type

杂志文章

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