Bianchi C P
Department of Pharmacology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, U.S.A.
Biochem Pharmacol. 1997 Apr 4;53(7):909-12. doi: 10.1016/s0006-2952(96)00711-3.
The ryanodine receptor (RyR) and the dihydropyridine (DHP) receptor (L-channels) comprise the main elements of the functional feet of the triadic element in skeletal muscle. These two main elements have conformational states that are regulated by the membrane potential and the consequent electrical field. The pharmacological action of ryanodine on skeletal muscle depends upon the physiological functional state of the RyR. At a resting potential of -90 m V, ryanodine at very low concentrations, 10(-11) M, causes the RyR to have a low conductance state which allows calcium to leak from the terminal cisternae of the sarcoplasmic reticulum and to be recycled with ATP utilization, leading to a marked increase in oxygen consumption and aerobic metabolism. At concentrations greater than 10(-6) M, ryanodine can cause a slowly developing contracture of resting muscle, inhibit the muscle twitch when the RyR complex is formed during stimulation, and, if formed before stimulation, accelerate the development of contracture. Biochemical studies have revealed that the RyR has four binding sites in which the conductance state depends upon the number of sites occupied by ryanodine. Our present understanding of the RyR-operated calcium channel is the result of an interdisciplinary approach in which each discipline (anatomy, physiology, biophysics, and biochemistry) contributes to our knowledge of the pharmacological action of ryanodine.
兰尼碱受体（RyR）和二氢吡啶（DHP）受体（L型通道）构成了骨骼肌三联体功能足的主要元件。这两个主要元件具有受膜电位及随之产生的电场调控的构象状态。兰尼碱对骨骼肌的药理作用取决于RyR的生理功能状态。在 -90 mV的静息电位下，极低浓度（10^(-11) M）的兰尼碱会使RyR处于低电导状态，允许钙从肌浆网终末池泄漏并通过ATP利用进行再循环，导致氧消耗和有氧代谢显著增加。在浓度高于10^(-6) M时，兰尼碱可导致静息肌肉缓慢发展为挛缩，在刺激过程中当RyR复合物形成时抑制肌肉抽搐，而如果在刺激前形成，则加速挛缩的发展。生化研究表明，RyR有四个结合位点，其电导状态取决于被兰尼碱占据的位点数量。我们目前对RyR操纵的钙通道的理解是跨学科方法的结果，其中每个学科（解剖学、生理学、生物物理学和生物化学）都为我们对兰尼碱药理作用的认识做出了贡献。
