Differences in L-type Ca2+ channel activity partially underlie the regional dichotomy in pumping behavior by murine peripheral and visceral lymphatic vessels.
Differences in L-type Ca2+ channel activity partially underlie the regional dichotomy in pumping behavior by murine peripheral and visceral lymphatic vessels.
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L 型 Ca2 通道活性的差异部分是小鼠外周和内脏淋巴管泵送行为的区域二分法的基础。
DOI：
10.1152/ajpheart.00499.2017
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Davis,MichaelJ
中科院分区：
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作者：
Zawieja,ScottD;Castorena-Gonzalez,JorgeA;Scallan,JoshuaP;Davis,MichaelJ
我们确定了小鼠淋巴管收缩功能在外周或内脏腔内血管位置方面的区域性二分法。在我们的体外等压肌图仪实验中，所有从周围区域分离的血管[颈、窝、腹股沟、腋窝和结间腹股沟腋窝(ING-Ax)]都表现出强烈的收缩，最大射血分数(EFS)为50-80%。相反，从内脏腔分离的血管(肠系膜、胸导管和髂动脉)显示最大≤为10%。通过压力肌图、尖端电极膜电位记录和钙离子成像，我们评估了L类钙通道在这种收缩二分法中的作用。ING-Ax膜电位显示一个~2-S动作电位(AP)周期(静息−35 mV，峰−5 mV，平台−11 mV)，平台期被L类钙通道激动剂BAY K8644显著延长。然而，从肠系膜血管记录的APS显示上升较慢，超过阈值的时间延长。Bayk(100 NM)使肠系膜AP上升速度和平台持续时间增加，但也使血管明显超极化。在这两个区域的血管收缩之前，都会出现钙闪光，这是用一种平滑肌特异的内源性钙离子报告程序检测到的，通常是在血管长度上协调进行的。与膜电位记录类似，肠系膜血管的钙闪烁较弱，上升时间较慢，但持续时间较长。百忧解(100 NM)可显著增加肠系膜血管钙瞬变幅度和持续时间，缩短肠系膜血管钙达峰时间。然而，需要更高浓度(1μM)的Bayk才能产生内脏淋巴管EF的轻微增加，内脏淋巴管的EF保持在20%。从小鼠外周组织分离的新淋巴管和非内脏淋巴管，表现出与其他动物模型和人类淋巴管相似的强烈收缩行为。这些差异的部分原因是L型钙通道的活性，如首次测量的小鼠淋巴动作电位和收缩相关的钙瞬变所揭示的那样。
We identified a regional dichotomy in murine lymphatic contractile function with regard to vessel location within the periphery or visceral cavity. All vessels isolated from peripheral regions [cervical, popliteal, inguinal, axillary, and internodal inguinal axillary (Ing-Ax)] developed robust contractions with maximal ejection fractions (EFs) of 50–80% in our ex vivo isobaric myograph experiments. Conversely, vessels isolated from the visceral cavity (mesenteric, thoracic duct, and iliac) demonstrated maximal EFs of ≤10%. Using pressure myography, sharp electrode membrane potential recordings, and Ca2+imaging, we assessed the role of L-type Ca2+channels in this contractile dichotomy. Ing-Ax membrane potential revealed a ~2-s action potential (AP) cycle (resting −35 mV, spike −5 mV, and plateau −11 mV) with a plateau phase that was significantly lengthened by the L-type Ca2+channel agonist Bay K8644 (BayK; 100 nM). APs recorded from mesenteric vessels, however, displayed a slower upstroke and an elongated time over threshold. BayK (100 nM) increased the mesenteric AP upstroke velocity and plateau duration but also significantly hyperpolarized the vessel. Contractions of vessels from both regions were preceded by Ca2+flashes, detected with a smooth muscle-specific endogenous Ca2+reporter, that typically were coordinated over the length of the vessel. Similar to the membrane potential recordings, Ca2+flashes in mesenteric vessels were weaker and had a slower rise time but were longer lasting than those in Ing-Ax vessels. BayK (100 nM) significantly increased the Ca2+transient amplitude and duration in both vessels and decreased time to peak Ca2+in mesenteric vessels. However, a higher concentration (1 μM) of BayK was required to produce even a modest increase in EF in visceral lymphatics, which remained at <20%.NEW & NOTEWORTHYLymphatic collecting vessels isolated from murine peripheral tissues, but not from the visceral cavities, display robust contractile behavior similar to lymphatic vessels from other animal models and humans. These differences are partially explained by L-type Ca2+channel activity as revealed by the first measurements of murine lymphatic action potentials and contraction-associated Ca2+transients.