Physiological Laboratory, University of Cambridge, England, UK.
J Gen Physiol. 2011 Jul;138(1):95-116. doi: 10.1085/jgp.201110617. Epub 2011 Jun 13.
Activation of skeletal muscle fibers requires rapid sarcolemmal action potential (AP) conduction to ensure uniform excitation along the fiber length, as well as successful tubular excitation to initiate excitation-contraction coupling. In our companion paper in this issue, Pedersen et al. (2011. J. Gen. Physiol. doi:10.1085/jgp.201010510) quantify, for subthreshold stimuli, the influence upon both surface conduction velocity and tubular (t)-system excitation of the large changes in resting membrane conductance (G(M)) that occur during repetitive AP firing. The present work extends the analysis by developing a multi-compartment modification of the charge-difference model of Fraser and Huang to provide a quantitative description of the conduction velocity of actively propagated APs; the influence of voltage-gated ion channels within the t-system; the influence of t-system APs on ionic homeostasis within the t-system; the influence of t-system ion concentration changes on membrane potentials; and the influence of Phase I and Phase II G(M) changes on these relationships. Passive conduction properties of the novel model agreed with established linear circuit analysis and previous experimental results, while key simulations of AP firing were tested against focused experimental microelectrode measurements of membrane potential. This study thereby first quantified the effects of the t-system luminal resistance and voltage-gated Na(+) channel density on surface AP propagation and the resultant electrical response of the t-system. Second, it demonstrated the influence of G(M) changes during repetitive AP firing upon surface and t-system excitability. Third, it showed that significant K(+) accumulation occurs within the t-system during repetitive AP firing and produces a baseline depolarization of the surface membrane potential. Finally, it indicated that G(M) changes during repetitive AP firing significantly influence both t-system K(+) accumulation and its influence on the resting membrane potential. Thus, the present study emerges with a quantitative description of the changes in membrane potential, excitability, and t-system ionic homeostasis that occur during repetitive AP firing in skeletal muscle.
骨骼肌纤维的激活需要快速的肌膜动作电位（AP）传导，以确保纤维长度上的均匀兴奋，以及成功的管状兴奋以启动兴奋-收缩偶联。在本期的伴生论文中，Pedersen 等人（2011. J. Gen. Physiol. doi:10.1085/jgp.201010510）量化了在亚阈刺激下，反复 AP 放电过程中静息膜电导（G(M)）的巨大变化对表面传导速度和管状（t）系统兴奋的影响。本工作通过开发 Fraser 和 Huang 的电荷差模型的多室修正版，对主动传播的 AP 的传导速度进行了定量描述；t 系统内电压门控离子通道的影响；t 系统 AP 对 t 系统内离子动态平衡的影响；t 系统离子浓度变化对膜电位的影响；以及 Phase I 和 Phase II G(M)变化对这些关系的影响。新型模型的被动传导特性与已建立的线性电路分析和先前的实验结果一致，而对 AP 放电的关键模拟则与针对膜电位的聚焦实验微电极测量进行了测试。因此，本研究首次量化了 t 系统管腔电阻和电压门控 Na(+)通道密度对表面 AP 传播和 t 系统产生的电响应的影响。其次，它证明了在反复 AP 放电过程中 G(M)变化对表面和 t 系统兴奋性的影响。第三，它表明，在反复 AP 放电过程中，大量的 K(+)在 t 系统内积累，导致表面膜电位的基线去极化。最后，它表明，在反复 AP 放电过程中 G(M)的变化显著影响 t 系统内的 K(+)积累及其对静息膜电位的影响。因此，本研究对骨骼肌反复 AP 放电过程中膜电位、兴奋性和 t 系统离子动态平衡的变化进行了定量描述。
