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Liu, M., Albert, A. P. 
ORCID: https://orcid.org/0000-0002-3596-9634 and Large, W. A.
(2005)
Facilitatory effect of Ins(1,4,5)P3 on store-operated Ca2+-permeable cation channels in rabbit portal vein myocytes.
Journal of Physiology, 566 (1).
pp. 161-171.
ISSN 0022-3751
Abstract
In rabbit portal vein smooth muscle cells, store-operated Ca2+-permeable cation channels (SOCs) display multi-modal gating mechanisms. SOCs are activated by depletion of intracellular Ca2+ 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)P3) modulates SOC activity in freshly dispersed rabbit portal vein myocytes with patch pipette recording techniques. Inclusion of 1 μM Ins(1,4,5)P3 in the patch pipette solution increased whole-cell currents evoked by the Ca2+-ATPase inhibitor cyclopiazonic acid (CPA) by about 3-fold at -80 mV. In the cell-attached configuration the cell-permeable Ca2+ chelator BAPTA-AM stimulated SOC activity and after excision of an isolated inside-out patch bath application of 1 μM Ins(1,4,5)P3 increased open channel probability (NPo) by approximately 3-fold. Ins(1,4,5)P3 also produced a similar increase in NPo 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)P3 on increasing PDBu-evoked SOC activity was about 0.4 μM. The facilitatory effect of Ins(1,4,5)P3 was also manifest as markedly increasing the rate of activation of SOCs. The synergistic effect of Ins(1,4,5)P3 was mimicked by the metabolically stable analogue 3-fluoro-Ins(1,4,5)P3 and Ins(1,4)P2, a metabolite of Ins(1,4,5)P3, but was not inhibited by the classical Ins(1,4,5)P3 receptor antagonist heparin. Finally Ins(1,4,5)P3 also increased NPo of SOCs activated by a PKC catalytic subunit. It is concluded that Ins(1,4,5)P3 facilitates SOC opening via a heparin-insensitive mechanism at, or dose to, the channel protein.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | physiology ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 29 Oct 2024 09:30 |
| Last Modified: | 03 Nov 2024 07:31 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97274 |
| DOI: | 10.1113/jphysiol.2005.088260 |
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