Gallant E M, Lentz L R, Taylor S R
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108, USA.
J Cell Physiol. 1995 Nov;165(2):254-60. doi: 10.1002/jcp.1041650206.
Caffeine contractures were induced after K(+)-conditioning of skeletal muscles from pigs and mice. K(+)-conditioning is defined as the partial depolarization caused by increasing external potassium (K+0) with [K+]x[Cl-] constant. Conditioning depolarizations that rendered muscles refractory to brief electrical stimulation still enhanced the contracture tension elicited by subsequent direct caffeine stimulation of sarcoplasmic reticulum (SR) calcium release. The effects of K(+)-conditioning on caffeine-induced contractures of intact cell bundles reached a maximum at 15-30 mM K+0 and then progressively declined at higher [K+]0. Conditioning with 30 mM K+ for 5 min, which inactivates excitation-contraction (EC) coupling in response to action potentials, both increased the magnitude of caffeine contractures 2-10-fold and shifted the contracture threshold toward lower caffeine concentrations. Enhanced sensitivity to caffeine was inhibited by dantrolene (20 microM) and its watersoluble analogue azumolene (150 microM). These drugs decreased caffeine-induced contractures following depolarization with 4-15 mM K+ to 25-50% of control tension. The inorganic anion perchlorate (CIO-4), which like caffeine potentiates twitches, increased caffeine-induced contractures approximately twofold after K(+)-conditioning (> 4 mM). The results suggest that CIO-4 and dantrolene, in addition to caffeine, also influence SR calcium release either directly or by mechanism(s) subsequent to depolarization of the sarcolemma. Moreover, since CIO-4 is known to shift the voltage-dependence of intramembrane charge movement, CIO-4 may exert effects on the transverse-tubule voltage sensors as well as the SR.
在对猪和小鼠的骨骼肌进行钾离子（K⁺）预处理后诱发了咖啡因挛缩。K⁺预处理定义为在[K⁺]×[Cl⁻]恒定的情况下，通过增加细胞外钾离子（K⁺₀）引起的部分去极化。使肌肉对短暂电刺激产生不应性的预处理去极化仍能增强随后直接用咖啡因刺激肌浆网（SR）释放钙所引发的挛缩张力。K⁺预处理对完整细胞束咖啡因诱发挛缩的影响在K⁺₀为15 - 30 mM时达到最大值，然后在更高的[K⁺]₀时逐渐下降。用30 mM K⁺预处理5分钟可使肌肉对动作电位的兴奋 - 收缩（EC）偶联失活，这既使咖啡因挛缩的幅度增加了2 - 10倍，又使挛缩阈值向更低的咖啡因浓度偏移。丹曲林（20 μM）及其水溶性类似物阿佐莫林（150 μM）可抑制对咖啡因的敏感性增强。这些药物在用4 - 15 mM K⁺去极化后，将咖啡因诱发的挛缩降低至对照张力的25 - 50%。无机阴离子高氯酸盐（ClO₄⁻）与咖啡因一样能增强抽搐，在K⁺预处理（> 4 mM）后使咖啡因诱发的挛缩增加约两倍。结果表明，除了咖啡因外，ClO₄⁻和丹曲林还可直接或通过肌膜去极化后的机制影响SR钙释放。此外，由于已知ClO₄⁻会改变膜内电荷移动的电压依赖性，所以ClO₄⁻可能对横管电压传感器以及SR都有作用。
