Copyright © 2005, European Society of Cardiology
Involvement of BKCa 
subunit tyrosine phosphorylation in vascular hyporesponsiveness of superior mesenteric artery following hemorrhagic shock in rats
State Key Laboratory of Trauma, Burns and Combined Injury, Department 2, Research Institute of Surgery, Daping Hospital, The Third Military Medical University, Daping, Chongqing 400042, PR China
* Corresponding author. Tel.: +86 23 68757452; fax: +86 23 68813806. Email address: liuliangming2002{at}yahoo.com
Objective: Vascular hyporesponsiveness is a major complication following severe trauma and shock. It plays important roles in the development of shock and seriously interferes with the treatment of shock. The mechanism responsible for the occurrence of vascular hyporesponsiveness has not been fully understood. The purpose of this study was to determine whether the 
subunit tyrosine sites of large conductance calcium-activated potassium channel (BKCa) could be phosphorylated and whether the phosphorylation of BKCa was closely associated with the activation of BKCa and the development of vascular hyporesponsiveness following hemorrhagic shock in rats.
Methods: A hemorrhagic shock (30 mm Hg for 0.5, 2, 4 h) model of Wistar rats was established. Phosphorylation of tyrosine residues of the BKCa subunit from vascular smooth muscle cells (VSMC) in superior mesenteric arteries (SMA) was detected by immunoprecipitation and Western blotting. BKCa activity was evaluated by cell-attached patch clamping. The vascular responsiveness of SMA to norepinephrine was measured with an isolated organ perfusion system.
Results: The level of BKCa subunit tyrosine phosphorylation was increased in a time-dependent manner following hemorrhagic shock, which was mediated by protein tyrosine kinases (PTK) and protein tyrosine phosphatases (PTP). The activation of VSMC BKCa following hemorrhagic shock was inhibited by genistein (2 x 10–5 mol/L), the permeable isoflavone PTK inhibitor, and was potentiated by the PTP inhibitor sodium orthovanadate (Na3VO4, 10–3 mol/L). The decreased vasoresponsiveness following hemorrhagic shock was partly restored by genistein (10–5 mol/L) or by the BKCa-selective inhibitor tetrabutylammonium chloride (0.1 mmol/L), while it was further decreased by Na3VO4 (10–5 mol/L).
Conclusion: The tyrosine residues of BKCa subunit of SMA were phosphorylated following hemorrhagic shock, which was regulated by PTK and PTP and appeared to be related to the activation of BKCa and the development of vascular hyporesponsiveness following hemorrhagic shock.
KEYWORDS Shock; Ion channel; Contractile function; Large conductance calcium activated potassium channel (BKCa); Tyrosine protein kinase
Time for primary review 32 days
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