Ryanodine: its alterations of cat papillary muscle contractile state and responsiveness to inotropic interventions and a suggested mechanism of action.
Ryanodine: its alterations of cat papillary muscle contractile state and responsiveness to inotropic interventions and a suggested mechanism of action.
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Ryanodine：它改变猫乳头肌收缩状态和对正性肌力干预的反应以及建议的作用机制。
DOI：
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发表时间：
1979
影响因子：
3.5
通讯作者：
H. R. Besch
中科院分区：
文献类型：
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作者：
J. Sutko;J. Willerson;G. Templeton;L. Jones;H. R. Besch
猫右心室乳头肌双相反应累积添加的兰尼定。在低至中等浓度（5 nM-1 μ M）的兰尼定下观察到进行性和显著的负性肌力作用，而当兰尼定浓度进一步增加至100 μ M时，这些初始变化恢复或逆转回到给药前值。主动力发展（DF），力发展率（dF/dt），以及松弛率都表现出这些双向变化。相比之下，在整个试验浓度范围内，达到峰值力的时间仅逐渐延长。在正常和K+去极化（异丙肾上腺素或二丁酰cAMP恢复）制剂中均观察到这种反应模式。在2.5 mM Ca++存在下，对单次加入100 μ M ryanodine的响应模拟了累积浓度响应曲线的定性和定量方面。在5.0 mM Ca++存在下，高浓度的ryanodine不再引起抑郁症，而是只引起缓慢发展的DF的双相增加。Ryanodine还改变了心室肌对其他正性肌力干预的反应。Ryanodine（1 μ M; 2.5mM Ca ~（++）可消除成对电刺激（PES）或50 mOsM甘露醇后dF/dt的正常增加，但不能消除加倍刺激频率（0.2- 0.4Hz）引起的dF/dt的正常增加。在兰尼碱暴露后，PES的开发力的增强从第一次（规则）到第二次（过早）收缩，产生一个求和样波形。预先加入钙离子通道拮抗剂D 600（1 μ M）并没有改变ryanodine诱导的PES变化。咖啡因（1 mM）产生的PES和高渗透压的反应，这是类似于与ryanodine观察到的改变。在高浓度的ryanodine（100 μ M）和钙（5 mM）存在下，对刺激率加倍（0.2- 0.4 Hz）的瞬时和稳态反应都被显著抑制，而通常伴随刺激率降低的DF或dF/dt的降低被减弱。在本研究中获得的数据是一致的功能抑制肌浆网钙释放的ryanodine。
Cat right ventricular papillary muscles responded biphasically to cumulative additions of ryanodine. A progressive and pronounced negative inotropic effect was observed with low to intermediate ryanodine concentrations (5 nM-1 muM) while a rebound or reversal of these initial changes back toward pre-drug values was obtained as the ryanodine concentration was further increased to 100 muM. Active force development (DF), the rate of force development (dF/dt), as well as the rate of relaxation all exhibited these bidirectional changes. In contrast, time to peak force underwent only a progressive prolongation over the entire concentration range tested. This response pattern was observed with both normal and K+-depolarized (isoproterenol- or dibutyryl cAMP-restored) preparations. The response to a single addition of 100 muM ryanodine, in the presence of 2.5 mM Ca++ mimicked both the qualitative and quantitative aspects of the cumulative concentration response curve. In the presence of 5.0 mM Ca++ the high concentration of ryanodine no longer caused depression but instead caused only a slowly developing, monophasic increase in DF. Ryanodine also changed the response of ventricular muscle to other inotropic interventions. Ryanodine (1 muM; 2.5 mM Ca++) abolished the normal increase in dF/dt following either paired electrical stimulation (PES) or 50 mOsM mannitol, but not that in response to a doubling of the stimulation rate (0.2--0.4 Hz). After ryanodine exposure, the potentiation of developed force by PES was shifted from the first (regular) to the second (premature) contraction, producing a summation-like waveform. Prior addition of the calcium channel antagonist D600 (1 muM) did not alter ryanodine-induced changes in PES. Caffeine (1 mM) produced alterations in the responses to PES and hyperosmolarity which were similar to those observed with ryanodine. In the presence of high concentrations of both ryanodine (100 muM) and calcium (5 mM) both the transient and steady-state responses to a doubling of the stimulation rate (0.2--0.4 Hz) were markedly depressed, whereas the decrease in DF or dF/dt normally accompanying a reduction in the rate of stimulation was attenuated. The data obtained in the present study are consistent with a functional inhibition of sarcoplasmic reticular calcium release by ryanodine.