Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart
Role of L-type calcium channels in pacing-induced short-term and long-term cardiac memory in canine heart
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DOI：
10.1161/01.cir.0000068376.88600.41
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发表时间：
2003-06-10
期刊：
影响因子：
37.8
通讯作者：
Rosen, MR
中科院分区：
文献类型：
--
作者：
Plotnikov, AN;Yu, HG;Rosen, MR
背景：我们测试了I-Ca，I-L对心脏记忆的发展很重要的假设。方法与结果：对急性麻醉犬和长期麻醉清醒犬进行l型Ca2+通道阻断和β -通道阻断试验。采用2 h心室起搏诱导短期记忆（STM）， 21 d心室起搏诱导长期记忆（LTM）。STM犬接受安慰剂、硝苯地平或心得安，LTM犬接受安慰剂、阿替洛尔或氨氯地平。在LTM中还检测了AT(1)受体阻断（坎地沙坦）和ACE抑制（曲多拉普利）。使用微电极记录分离心外膜和心内膜板的跨膜电位，采用模拟完整动物STM的方案。分离LTM或假对照犬的左心室心外膜肌细胞，记录I-Ca、I-L（全细胞膜片钳技术）。I-Ca、I-L阻滞剂对STM和LTM的进化有抑制作用，而β -阻滞剂对STM和LTM没有抑制作用。AT(1)受体阻断和ACE抑制均未抑制LTM。在微电极实验中，起搏诱导的心外膜-心内膜梯度变化与STM相似，但硝苯地平抑制了这种变化。膜片钳实验中，LTM与对照组的I-Ca峰、I-L密度相当，但LTM的激活更阳性，失活时间常数更长（P < 0.05）。结论i - ca、I-L阻断对心脏记忆有抑制作用，β-肾上腺素能阻断对心脏记忆无抑制作用。LTM的进化不受血管紧张素II阻断的影响，并与I-Ca、I-L动力学的改变有关。
Background-We tested the hypothesis that I-Ca,I-L is important to the development of cardiac memory.Methods and Results-The effects of L-type Ca2+ channel blockade and beta-blockade were tested on acutely anesthetized and on chronically instrumented, conscious dogs. Short-term memory (STM) was induced by 2 hours of ventricular pacing and long-term memory (LTM) by ventricular pacing for 21 days. STM dogs received placebo, nifedipine, or propranolol, and LTM dogs received placebo, atenolol, or amlodipine. AT(1) receptor blockade (candesartan) and ACE inhibition (trandolapril) were also tested in LTM. Microelectrodes were used to record transmembrane potentials from isolated epicardial and endocardial slabs using a protocol simulating STM in intact animals. Left ventricular epicardial myocytes from LTM or sham control dogs were dissociated, and I-Ca,I-L was recorded (whole-cell patch-clamp technique). Evolution of STM and LTM was attenuated by I-Ca,I-L blockers but not beta-blockers. Neither AT(1) receptor blockade nor ACE inhibition suppressed LTM. In microelectrode experiments, pacing induced an epicardial-endocardial gradient change mimicking STM that was suppressed by nifedipine. In patch-clamp experiments, peak I-Ca,I-L density in LTM and control were equivalent, but activation was more positive and time constants of inactivation longer in LTM (P < 0.05).Conclusions-I-Ca,I-L blockade but not β-adrenergic blockade suppresses cardiac memory. LTM evolution is unaffected by angiotensin II blockade and is associated with altered I-Ca,I-L kinetics.