Percival A L, Williams A J, Kenyon J L, Grinsell M M, Airey J A, Sutko J L
Department of Pharmacology, University of Nevada School of Medicine, Reno 89557.
Biophys J. 1994 Nov;67(5):1834-50. doi: 10.1016/S0006-3495(94)80665-4.
To define the roles of the alpha- and beta-ryanodine receptor (RyR) (sarcoplasmic reticulum Ca2+ release channel) isoforms expressed in chicken skeletal muscles, we investigated the ion channel properties of these proteins in lipid bilayers. alpha- and beta RyRs embody Ca2+ channels with similar conductances (792, 453, and 118 pS for K+, Cs+ and Ca2+) and selectivities (PCa2+/PK+ = 7.4), but the two channels have different gating properties. alpha RyR channels switch between two gating modes, which differ in the extent they are activated by Ca2+ and ATP, and inactivated by Ca2+. Either mode can be assumed in a spontaneous and stable manner. In a low activity mode, alpha RyR channels exhibit brief openings (tau o = 0.14 ms) and are minimally activated by Ca2+ in the absence of ATP. In a high activity mode, openings are longer (tau o1-3 = 0.17, 0.51, and 1.27 ms), and the channels are activated by Ca2+ in the absence of ATP and are in general less sensitive to the inactivating effects of Ca2+. beta RyR channel openings are longer (tau 01-3 = 0.34, 1.56, and 3.31 ms) than those of alpha RyR channels in either mode. beta RyR channels are activated to a greater relative extent by Ca2+ than ATP and are inactivated by millimolar Ca2+ in the absence, but not the presence, of ATP. Both alpha- and beta RyR channels are activated by caffeine, inhibited by Mg2+ and ruthenium red, inactivated by voltage (cytoplasmic side positive), and modified to a long-lived substate by ryanodine, but only alpha RyR channels are activated by perchlorate anions. The differences in gating and responses to channel modifiers may give the alpha- and beta RyRs distinct roles in muscle activation.
为了确定在鸡骨骼肌中表达的α-和β-兰尼碱受体（RyR）（肌浆网Ca2+释放通道）亚型的作用，我们研究了这些蛋白在脂质双分子层中的离子通道特性。α-和β-RyRs体现出具有相似电导（K+、Cs+和Ca2+的电导分别为792、453和118 pS）和选择性（PCa2+/PK+ = 7.4）的Ca2+通道，但这两种通道具有不同的门控特性。α-RyR通道在两种门控模式之间切换，这两种模式在被Ca2+和ATP激活的程度以及被Ca2+失活的程度上有所不同。两种模式都可以以自发且稳定的方式呈现。在低活性模式下，α-RyR通道表现出短暂开放（τo = 0.14毫秒），并且在没有ATP的情况下被Ca2+最小程度地激活。在高活性模式下，开放时间更长（τo1 - 3 = 0.17、0.51和1.27毫秒），并且通道在没有ATP的情况下被Ca2+激活，并且总体上对Ca2+的失活作用不太敏感。β-RyR通道的开放时间比α-RyR通道在任何一种模式下的开放时间都长（τ01 - 3 = 0.34、1.56和3.31毫秒）。β-RyR通道被Ca2+激活的相对程度大于被ATP激活的程度，并且在没有ATP但存在ATP时不会被毫摩尔浓度的Ca2+失活。α-和β-RyR通道都被咖啡因激活，被Mg2+和钌红抑制，被电压（细胞质侧为正）失活，并且被兰尼碱修饰为一种长寿的亚状态，但只有α-RyR通道被高氯酸根阴离子激活。门控和对通道调节剂反应的差异可能使α-和β-RyRs在肌肉激活中发挥不同的作用。
