Facilitatory effect of Ins(1,4,5) P 3 on store‐operated Ca 2+ ‐permeable cation channels in rabbit portal vein myocytes
In rabbit portal vein smooth muscle cells, store‐operated Ca 2+ ‐permeable cation channels (SOCs) display multi‐modal gating mechanisms. SOCs are activated by depletion of intracellular Ca 2+ stores but also may be stimulated in a store‐independent manner by noradrenaline acting on α‐adrenoceptors a...
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Published in | The Journal of physiology Vol. 566; no. 1; pp. 161 - 171 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
01.07.2005
|
Online Access | Get full text |
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Summary: | In rabbit portal vein smooth muscle cells, store‐operated Ca
2+
‐permeable cation channels (SOCs) display multi‐modal gating mechanisms. SOCs are activated by depletion of intracellular Ca
2+
stores but also may be stimulated in a store‐independent manner by noradrenaline acting on α‐adrenoceptors and by diacylglycerol (DAG) via protein kinase C (PKC). In the present study we have investigated whether inositol 1,4,5‐trisphosphate (Ins(1,4,5)
P
3
) modulates SOC activity in freshly dispersed rabbit portal vein myocytes with patch pipette recording techniques. Inclusion of 1 μ
m
Ins(1,4,5)
P
3
in the patch pipette solution increased whole‐cell currents evoked by the Ca
2+
‐ATPase inhibitor cyclopiazonic acid (CPA) by about 3‐fold at −80 mV. In the cell‐attached configuration the cell‐permeable Ca
2+
chelator BAPTA‐AM stimulated SOC activity and after excision of an isolated inside‐out patch bath application of 1 μ
m
Ins(1,4,5)
P
3
increased open channel probability (
NP
o
) by approximately 3‐fold. Ins(1,4,5)
P
3
also produced a similar increase in
NP
o
of SOCs stimulated by the phorbol ester, phorbol 12,13‐dibutyrate (PDBu) in inside‐out patches and these channel currents had a unitary conductance of about 2 pS. The equilibrium constant of Ins(1,4,5)
P
3
on increasing PDBu‐evoked SOC activity was about 0.4 μ
m
. The facilitatory effect of Ins(1,4,5)
P
3
was also manifest as markedly increasing the rate of activation of SOCs. The synergistic effect of Ins(1,4,5)
P
3
was mimicked by the metabolically stable analogue 3‐fluoro‐Ins(1,4,5)
P
3
and Ins(1,4)
P
2
, a metabolite of Ins(1,4,5)
P
3
, but was not inhibited by the classical Ins(1,4,5)
P
3
receptor antagonist heparin. Finally Ins(1,4,5)
P
3
also increased
NP
o
of SOCs activated by a PKC catalytic subunit. It is concluded that Ins(1,4,5)
P
3
facilitates SOC opening via a heparin‐insensitive mechanism at, or close to, the channel protein. |
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ISSN: | 0022-3751 1469-7793 |
DOI: | 10.1113/jphysiol.2005.088260 |