Hamrell B B, Dey S K
Department of Molecular Physiology and Biophysics, College of Medicine, UVM Medical Research Facility, Colchester, VT 05446-2500.
J Mol Cell Cardiol. 1993 Dec;25(12):1483-500. doi: 10.1006/jmcc.1993.1164.
Earlier we noted the importance of internal loads for sarcomere shortening in heart muscle. Internal loading may change with hypertrophy and influence sarcomere shortening velocity. Therefore, we force clamped trabeculae from normal rabbit right ventricles and those hypertrophied due to pulmonary artery constriction. Diffraction of a laser (lambda = 632.8 nm) by a trabecula was used to measure sarcomere length (SL) in isotonic twitches. Resting SL was set at 2.36 +/- 0.17 microns in the normal (n = 5) and 2.23 +/- 0.08 microns in the hypertrophied (n = 5) (+/- S.E.M.) muscles. The relationship of total stress with log10 sarcomere shortening velocity was linear. In the normals, log(SL/s) = 0.39-1.32 (P(total)/P(isom)), and in hypertrophy, log(SL/s) = -0.16-0.57 (P(total)/P(isom)). SL/s is sarcomere shortening velocity in microns/s divided by SL at the onset of constant force. P(total) is isotonic plus resting stress and P(isom) is peak total isometric stress. The hypertrophy (P(total)/P(isom))-(SL/s) relationship is depressed below normal at low loads (P < 0.001). Estimated unloaded SL/s in the normals was 2.47 and 0.69 in hypertrophy. Paired stimulation had no effect on normal SL/s. In hypertrophy, paired stimulation increased SL/s at low loads to normal levels. Thus, depressed sarcomere shortening velocity at low loads in hypertrophy at physiological sarcomere lengths disappeared when myoplasmic [Ca2+] increased. The results suggested that internal loading was greater than normal during shortening of hypertrophied myocardium. Increased myoplasmic [Ca2+] increased the number of crossbridges and reduced the load per crossbridge. This was a likely mechanism for the increase of sarcomere shortening velocity to normal levels.
之前我们提到了心肌肌节缩短时内部负荷的重要性。内部负荷可能会随着心肌肥厚而改变，并影响肌节缩短速度。因此，我们对正常兔右心室以及因肺动脉狭窄而肥厚的小梁进行强制钳夹。利用小梁对激光（波长λ = 632.8 nm）的衍射来测量等张收缩时的肌节长度（SL）。正常组（n = 5）静息SL设定为2.36±0.17微米，肥厚组（n = 5）静息SL设定为2.23±0.08微米（±标准误）。总应力与log10肌节缩短速度的关系呈线性。正常组中，log（SL/s） = 0.39 - 1.32（P（总）/P（等长）），肥厚组中，log（SL/s） = -0.16 - 0.57（P（总）/P（等长））。SL/s是肌节缩短速度（微米/秒）除以恒力开始时的SL。P（总）是等张加静息应力，P（等长）是峰值总等长应力。在低负荷时，肥厚组的（P（总）/P（等长））-（SL/s）关系低于正常水平（P < 0.001）。正常组估计的无负荷SL/s为2.47，肥厚组为0.69。成对刺激对正常组的SL/s无影响。在肥厚组中，成对刺激使低负荷时的SL/s增加至正常水平。因此，当肌浆[Ca2+]增加时，生理肌节长度下肥厚心肌低负荷时肌节缩短速度降低的现象消失。结果表明，肥厚心肌缩短过程中的内部负荷大于正常情况。肌浆[Ca2+]增加会增加横桥数量并降低每个横桥的负荷。这可能是肌节缩短速度增加至正常水平的机制。
