Ca2+ channels, ryanodine receptors and Ca(2+)-activated K+ channels: a functional unit for regulating arterial tone.
Ca2+ channels, ryanodine receptors and Ca(2+)-activated K+ channels: a functional unit for regulating arterial tone.
复制标题
DOI：
10.1046/j.1365-201x.1998.00462.x
复制
发表时间：
1998-12
期刊：
影响因子：
--
通讯作者：
J. Jaggar;G. Wellman;T. Heppner;V. Porter;G. Pérez;M. Gollasch;T. Kleppisch;M. Rubart;A. Stevenson;W. J. Lederer;H. Knot;A. Bonev;M. Nelson
中科院分区：
文献类型：
--
作者：
J. Jaggar;G. Wellman;T. Heppner;V. Porter;G. Pérez;M. Gollasch;T. Kleppisch;M. Rubart;A. Stevenson;W. J. Lederer;H. Knot;A. Bonev;M. Nelson
局部钙瞬变(钙火花)被认为是心脏、骨骼和平滑肌细胞中的基本钙信号。Ca~(2+)火花源于肌浆网(SR)中单个或多个紧密聚集的兰尼定受体(RyR)通道的协同开放。在动脉平滑肌中，钙火花似乎参与了对抗血管紧张性收缩的过程。血管内压引起约-40 mV的梯度膜电位去极化，动脉壁[Ca~(2+)]i升高和动脉收缩(肌源性张力)。Ca~(2+)火花激活肌膜上的钙敏感钾通道，引起膜超极化，与压力引起的去极化相反。因此，兰诺定抑制Ca~(2+)放电或Iberiooxin抑制Kca通道，导致膜去极化，激活L型电压门控性Ca~(2+)通道，血管收缩。相反，钙火花的激活可以通过激活KCA通道而导致血管扩张。我们最近的工作旨在研究钙离子火花在动脉平滑肌功能调节中的性质和作用。我们将探讨膜电位、环核苷酸和蛋白激酶C对钙离子触发频率和幅度的调节。通过电压依赖性钙离子通道的局部钙离子进入在调节钙离子火花特性中的作用也将被研究。最后，利用来自心肌细胞的功能证据和来自平滑肌的组织学证据，我们将探索钙通道、RyR通道和KCA通道是否作为一个耦合单位，通过钙和电压来调节动脉平滑肌膜电位和血管张力。
Local calcium transients ('Ca2+ sparks') are thought to be elementary Ca2+ signals in heart, skeletal and smooth muscle cells. Ca2+ sparks result from the opening of a single, or the coordinated opening of many, tightly clustered ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR). In arterial smooth muscle, Ca2+ sparks appear to be involved in opposing the tonic contraction of the blood vessel. Intravascular pressure causes a graded membrane potential depolarization to approximately -40 mV, an elevation of arterial wall [Ca2+]i and contraction ('myogenic tone') of arteries. Ca2+ sparks activate calcium-sensitive K+ (KCa) channels in the sarcolemmal membrane to cause membrane hyperpolarization, which opposes the pressure induced depolarization. Thus, inhibition of Ca2+ sparks by ryanodine, or of KCa channels by iberiotoxin, leads to membrane depolarization, activation of L-type voltage-gated Ca2+ channels, and vasoconstriction. Conversely, activation of Ca2+ sparks can lead to vasodilation through activation of KCa channels. Our recent work is aimed at studying the properties and roles of Ca2+ sparks in the regulation of arterial smooth muscle function. The modulation of Ca2+ spark frequency and amplitude by membrane potential, cyclic nucleotides and protein kinase C will be explored. The role of local Ca2+ entry through voltage-dependent Ca2+ channels in the regulation of Ca2+ spark properties will also be examined. Finally, using functional evidence from cardiac myocytes, and histological evidence from smooth muscle, we shall explore whether Ca2+ channels, RyR channels, and KCa channels function as a coupled unit, through Ca2+ and voltage, to regulate arterial smooth muscle membrane potential and vascular tone.