Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice.

Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice.
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PMCA 亚型在膀胱平滑肌 Ca2 稳态中的独特作用:来自 PMCA 基因消除小鼠的证据。

DOI:
10.1152/ajpcell.00313.2006
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发表时间:
2007
期刊:
American journal of physiology. Cell physiology
影响因子:
--
通讯作者:
Paul,RichardJ
Paul,RichardJ
中科院分区:
--
文献类型:
--
作者:
Liu,Li;Ishida,Yukisato;Okunade,Gbolahan;Pyne-Geithman,GailJ;Shull,GaryE;Paul,RichardJ

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我们以前表明,质膜Ca ~(2+)-ATP酶(PMCA)活性占膀胱平滑肌松弛的25-30%。在四种PMCA亚型中,只有PMCA 1和PMCA 4在平滑肌中表达。为了说明这些亚型的作用,我们使用fura-PE 3测量了胞浆Ca 2+([Ca 2 +]i),同时测量了野生型(WT)、Pmca 1 +/−、Pmca 4 +/−、Pmca 4 −/−和Pmca 1 +/− Pmca 4 −/−小鼠膀胱平滑肌的收缩性。膀胱制备物之间的基础[Ca 2 +] i值无差异。KCl(80 mM)在Pmca 1 +/−和Pmca 1 +/− Pmca 4 −/−膀胱平滑肌中引起的力(150-190%)和[Ca 2 +]i(130-180%)均大于WT或Pmca 4 −/−膀胱平滑肌中的力和[Ca 2 +] i。Pmca 1 +/−(120-150%)膀胱对卡巴胆碱(CCh:10 μM)的反应也高于WT膀胱。相反,Pmca 4-/-和Pmca 1 +/-Pmca 4-/-膀胱对CCh的反应明显小于WT(40-50%)。在Pmca 4 −/−(130-190%)和Pmca 1 +/− Pmca 4 −/−(120-250%)膀胱中,KCl和CCh引起的力和[Ca 2 +] i增加的半衰期以及激动剂洗脱后相应的力和[Ca 2 +] i减少的半衰期延长,但与WT相比,Pmca 1 +/−膀胱中的力和[Ca 2 +] i增加的半衰期未延长。我们的证据表明,不同的亚型功能与PMCA 1亚型参与整体Ca 2+清除,而PMCA 4是必不可少的[Ca 2 +] i增加和收缩反应的CCh受体介导的信号转导途径。
We previously showed that plasma membrane Ca2+-ATPase (PMCA) activity accounted for 25–30% of relaxation in bladder smooth muscle . Among the four PMCA isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role of these isoforms, we measured cytosolic Ca2+([Ca2+]i) using fura-PE3 and simultaneously measured contractility in bladder smooth muscle from wild-type (WT),Pmca1+/−,Pmca4+/−,Pmca4−/−, andPmca1+/−Pmca4−/−mice. There were no differences in basal [Ca2+]ivalues between bladder preparations. KCl (80 mM) elicited both larger forces (150–190%) and increases in [Ca2+]i(130–180%) in smooth muscle fromPmca1+/−andPmca1+/−Pmca4−/−bladders than those in WT orPmca4−/−. The responses to carbachol (CCh: 10 μM) were also greater inPmca1+/−(120–150%) than in WT bladders. In contrast, the responses inPmca4−/−andPmca1+/−Pmca4−/−bladders to CCh were significantly smaller (40–50%) than WT. The rise in half-times of force and [Ca2+]iincreases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged inPmca4−/−(130–190%) andPmca1+/−Pmca4−/−(120–250%) bladders, but not inPmca1+/−bladders with respect to WT. Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca2+clearance, while PMCA4 is essential for the [Ca2+]iincrease and contractile response to the CCh receptor-mediated signal transduction pathway.
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