Roles of Cl- channels and Ca2+ mobilization in stretch-induced increase of SA node pacemaker activity
Roles of Cl- channels and Ca2+ mobilization in stretch-induced increase of SA node pacemaker activity
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DOI：
10.1152/ajpheart.1996.270.5.h1726
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发表时间：
1996-05-01
影响因子：
4.8
通讯作者：
Toyama, J
中科院分区：
文献类型：
--
作者：
Arai, A;Kodama, I;Toyama, J
在兔离体窦房结上，研究了机械牵张增强心脏起搏活动的离子机制。用机械刺激器将0.2~2.0g的5-S伸展到SA结节的小组织条(1.5 mm×3.0 mm)上。用高增益放大的改良双极电极记录心内膜表面电位，监测自发兴奋周期长度(SPCL)。阿托品和心得安可消除神经末梢释放的神经递质的影响。拉伸0.2g可使SPCL显著缩短，SPCL最大缩短与牵引力呈正相关。用Gd(10mM)或格列本脲(1mM)处理该制剂不影响力-反应关系。4，4‘-二硝基二苯乙烯-2，2’-二磺酸(5 MM)、4-acetamido-4‘-isothiocyanostilbene-2，2’-disulfonic酸(1 MM)或4，4‘-二异硫氰基二苯乙烯-2，2’-二磺酸(50 MM)对机械牵张-GT；0.5g的正性变时性反应显著降低。这种正性变时性反应在低钙(0.36 mM)介质中也被减弱，并被兰尼定(0.1mM)或塔普西林(2mM)浸泡。这些结果提示，机械敏感的氯离子通道和细胞内钙动员可能参与了牵张引起的哺乳动物SA结节起搏活动的增强，尽管不能排除其他可能的机制。
Ionic mechanisms underlying the enhancement of cardiac pacemaking activity by mechanical stretch were investigated in the isolated rabbit sinoatrial (SA) node. A 5-s stretch of 0.2-2.0 g was applied to small tissue strips (1.5 mm x 3.0 mm) of the SA node using a mechanical stimulator. Spontaneous excitation cycle length (SPCL) was monitored by recording endocardial surface potential through modified bipolar electrodes with high-gain amplification. Influence of neurotransmitters released from nerve terminals was eliminated by atropine and propranolol. A stretch >0.2 g caused a significant shortening of SPCL; there was a positive correlation between the force and the maximum shortening of SPCL. Treatment of the preparation with gadolinium (10 mu M) or glibenclamide (1 mu M) did not affect the force-response relationship. The positive chronotropic response to mechanical stretch >0.5 g was reduced significantly by treatment with 4,4'-dinitrostilbene-2,2'-disulfonic acid (5 mM), 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (1 mM), or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (50 mu M). The positive chronotropic response was also reduced in a low-Ca2+ (0.36 mM) medium and by bath application of ryanodine (0.1 mu M) or thapsigargin (2 mu M) These findings suggest the possible involvement of mechanosensitive Cl- channels and intracellular Ca2+ mobilization in the stretch-induced enhancement of pacemaking activity in the mammalian SA node, although other conceivable mechanisms cannot be ruled out.