RATIO OF RYANODINE TO DIHYDROPYRIDINE RECEPTORS IN CARDIAC AND SKELETAL-MUSCLE AND IMPLICATIONS FOR E-C COUPLING
RATIO OF RYANODINE TO DIHYDROPYRIDINE RECEPTORS IN CARDIAC AND SKELETAL-MUSCLE AND IMPLICATIONS FOR E-C COUPLING
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DOI：
10.1152/ajpcell.1993.264.6.c1587
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发表时间：
1993-06-01
影响因子：
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通讯作者：
STIFFEL, VM
中科院分区：
文献类型：
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作者：
BERS, DM;STIFFEL, VM
我们测量了兔、大鼠、雪貂、豚鼠以及兔心室匀浆、骨骼肌匀浆和分离的三联肌的分离心室肌细胞中二氢苯胺受体（DHPR）和瑞安定受体（RYR）的密度。骨骼肌匀浆和三联肌的RYR/DHPR比值分别为0.7和0.52。这种化学统计与骨骼肌的兴奋-收缩（E-C）耦合模型相当一致，其中DHPR分子本身可能将Ca释放信号传递到肌浆网（SR），并且与B. A. Block、T. Imagawa、K. P. Campbell和C. Franzini-Armstrong在超微结构研究中提出的蟾蜍鱼囊的分子排列一致。[j] .中国生物医学工程学报，2009,31(2):387 - 396。也就是说，在一个有组织的阵列中，每四个DHPR大约有两个RYR，或者每个DHPR四分体有两个RYR脚（假设1个高亲和的RYR/脚和4个DHPR/四分体）。假设RYR和DHPR是心室肌细胞的有用标记物，但不是心室肌细胞的唯一标记物，我们也估计了兔心室肌细胞蛋白的比例（小于或等于55-62%）。心肌细胞的RYR/DHPR远高于骨骼肌细胞，并且在不同的哺乳动物肌细胞中存在差异。兔的RYR/DHPR比值为3.7，豚鼠为4.3，大鼠为7.3，雪貂为10.2。与骨骼肌相比，这些结果表明，心肌中每DHPR有更多的RYR足，这一比例取决于物种（即，每假定的DHPR四分体4-10倍，如果哺乳动物心脏中存在这种结构，则将高出4倍）。RYR与DHPR的高比值表明心肌中的大部分RYR不能与DHPR进行化学计量。因此，骨骼肌类型的E-C耦合几何结构不适用于心肌。此外，一个肌层钙通道必须控制许多SR钙释放通道（例如，如果所有通道都是活跃的，则通过钙诱导的钙释放）。这对心脏E-C耦合模型施加了物理限制。
We measured dihydropryidine receptor (DHPR) and ryanodine receptor (RYR) density in isolated ventricular myocytes from rabbits, rats, ferrets, and guinea pigs and also from rabbit ventricular homogenate, skeletal muscle homogenate, and isolated triads. In skeletal muscle homogenate and triads the RYR/DHPR ratio was 0.7 and 0.52, respectively. This stoichiometry is reasonably consistent with excitation-contraction (E-C) coupling models in skeletal muscle where the DHPR molecule itself may transmit the signal for Ca release to the sarcoplasmic reticulum (SR) and with the molecular arrangement proposed for toadfish swim-bladder from ultrastructural studies by B. A. Block, T. Imagawa, K. P. Campbell, and C. Franzini-Armstrong. (J. Cell Biol. 107: 2587-2600, 1988). That is, there could be approximately two RYR for each four DHPR or two RYR feet per DHPR tetrad in an organized array (assuming 1 high-affinity RYR/foot and 4 DHPR/tetrad). The fraction of rabbit ventricular protein that is cardiac myocyte protein was also estimated (less-than-or-equal-to 55-62%), assuming that RYR and DHPR are useful but not exclusive markers for myocytes in the ventricle. In cardiac myocytes the RYR/DHPR was much higher than in skeletal muscle and varied among different mammalian myocytes. The RYR/DHPR ratios were 3.7 in rabbit, 4.3 in guinea pig, 7.3 in rat, and 10.2 in ferret myocytes. In contrast to skeletal muscle, these results indicate that there are many more RYR feet per DHPR in cardiac muscle, and this ratio depends on species (i.e., 4-10 times and would be 4 times higher still per putative DHPR tetrad if that structure exists in mammalian heart). The high ratio of RYR to DHPR implies that most of the RYR in cardiac muscle cannot be stoichiometrically associated with DHPR. Thus a skeletal muscle type of E-C coupling geometry would not work for cardiac muscle. Furthermore, one sarcolemmal Ca channel would have to control many SR Ca release channels (e.g., via Ca-induced Ca release if all are active). This places physical constraints on models of cardiac E-C coupling.