Boulos P T, Heiman-Patterson T D, Alexander G M, Tahmoush A J
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Muscle Nerve. 2000 Nov;23(11):1736-47. doi: 10.1002/1097-4598(200011)23:11<1736::aid-mus10>3.0.co;2-1.
Paramyotonia congenita (PC) is an autosomal-dominant disorder due to a point mutation in the adult skeletal muscle Na channel gene. Muscle fibers from PC patients have normal membrane properties at 32 degrees C. At 27 degrees C, they are inexcitable, have increased Na conductance, and have a reduced resting membrane potential of -40 mV. To define the biophysical basis for the muscle membrane abnormalities, we performed patch clamp whole-cell and outside-out single Na channel studies at 22 degrees C on cultured human muscle cells from 4 control patients and 2 sisters with PC and the thr1313met mutant Na channel. The whole-cell studies showed no difference in window currents. Unlike cells transfected with the thr1313met mutant Na channel, the inactivation time constant, tau(h), for PC cells was similar to control cells. For PC recordings containing long-duration single Na channel openings, mean open time was prolonged at -60, -40, and -20 mV. The long-duration Na channel openings occurred randomly with no evidence of modal gating. The number of channel openings, occurrence of late openings, and the prolonged mean open time resulted in a sustained inward Na current at -40 mV. We suggest that the biophysical marker of the thr1313met mutant Na channel is a voltage- and temperature-dependent abnormality in mutant single Na channel behavior.
先天性副肌强直（PC）是一种常染色体显性疾病，由成人骨骼肌钠通道基因的点突变引起。PC患者的肌纤维在32℃时具有正常的膜特性。在27℃时，它们无法兴奋，钠电导增加，静息膜电位降低至-40 mV。为了确定肌膜异常的生物物理基础，我们在22℃下对4名对照患者和2名患有PC的姐妹以及携带thr1313met突变钠通道的培养人肌肉细胞进行了膜片钳全细胞和外翻式单钠通道研究。全细胞研究显示窗口电流没有差异。与转染了thr1313met突变钠通道的细胞不同，PC细胞的失活时间常数tau(h)与对照细胞相似。对于包含长时间单钠通道开放的PC记录，在-60 mV、-40 mV和-20 mV时平均开放时间延长。长时间的钠通道开放随机发生，没有模式门控的证据。通道开放的数量、晚期开放的发生以及延长的平均开放时间导致在-40 mV时出现持续的内向钠电流。我们认为，thr1313met突变钠通道的生物物理标志物是突变单钠通道行为中电压和温度依赖性异常。
