Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins
Novel Perspectives on Cardiac Pacemaker Regulation: Role of the Coupled Function of Sarcolemmal and Intracellular Proteins
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DOI：
10.1007/978-3-642-17575-6_4
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Lakatta, Edward G.
中科院分区：
文献类型：
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作者：
Maltsev, Victor A.;Vinogradova, Tatiana M.;Lakatta, Edward G.
最近的实验和理论研究表明，窦房结细胞（SANC）是心脏的主要起搏细胞，作为功能耦合的肌膜蛋白和细胞内蛋白的复杂系统发挥作用。该系统的蛋白质通过膜电压和局部肌膜下 Ca2+ 变化在整个起搏器周期中动态（逐次搏动）相互作用。此外，肌膜 (SL) 生电蛋白和肌浆网 (SR) Ca2+ 循环蛋白的功能通过 Ca2+-、PKA- 和 CaMKII 依赖性蛋白磷酸化进行偶联和酶调节。该系统不仅稳健（即在宽参数范围内故障安全），而且同时灵活，因为通过 G 蛋白偶联受体 (GPCR) 信号传导对搏动速率的自主神经调节作用于确保和调节基础状态下稳健的系统功能的完全相同的调节因子（即耦合因子、Ca2+、PKA 和 CaMKII）。本章总结了这种新颖的起搏器概念的实验和理论证据。
Recent experimental and theoretical studies demonstrate that the sinoatrial node cells (SANCs), the primary pacemaker cells of heart, operate as a complex system of functionally coupled sarcolemmal and intracellular proteins. The proteins of this system dynamically (beat-to-beat) interact throughout the entire pacemaker cycle via membrane voltage and local subsarcolemmal Ca2+changes. Furthermore, functions of the sarcolemmal (SL) electrogenic proteins and sarcoplasmic reticulum (SR) Ca2+cycling proteins are coupled and regulated enzymatically via Ca2+-, PKA-, and CaMKII-dependent protein phosphorylation. The system is not only robust (i.e., fail-safe within wide parameter range), but simultaneously flexible, because the autonomic neural modulation of the beating rate, via G protein-coupled receptor (GPCR) signaling, acts upon the very same regulatory factors (i.e., the coupling factors, Ca2+, PKA, and CaMKII) that ensure and regulate robust system function in the basal state. This chapter summarizes the experimental and theoretical evidences for this novel pacemaker concept.