Brief report - Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel
Brief report - Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel
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DOI：
10.1056/nejmoa052475
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发表时间：
2006-01-12
影响因子：
158.5
通讯作者：
DiFrancesco, D
中科院分区：
文献类型：
--
作者：
Milanesi, R;Baruscotti, M;DiFrancesco, D
我们发现，一个大家庭成员的窦性心动过缓与起搏器 HCN4 离子通道的基因编码突变有关。窦房结的起搏器通道产生自发活动并介导环磷酸腺苷 (cAMP) 依赖性心率自主调节。与心动过缓相关的突变位于 cAMP 结合位点附近；功能分析发现，突变型通道对 cAMP 反应正常，但在比野生型通道更负的电压下被激活。这些变化模仿了轻度迷走神经刺激，通过减少向内舒张电流来增加心率。因此，起搏器通道功能减弱与家族性心动过缓有关。
We found that sinus bradycardia in members of a large family was associated with a mutation in the gene coding for the pacemaker HCN4 ion channel. Pacemaker channels of the sinoatrial node generate spontaneous activity and mediate cyclic AMP (cAMP)-dependent autonomic modulation of the heart rate. The mutation associated with bradycardia is located near the cAMP-binding site; functional analysis found that mutant channels respond normally to cAMP but are activated at more negative voltages than are wild-type channels. These changes, which mimic those of mild vagal stimulation, sow the heart rate by decreasing the inward diastolic current. Thus, diminished function of pacemaker channels is linked to familial bradycardia.