A simple electrostatic model can explain the effect of pH upon the force-pCa relation of skinned frog skeletal muscle fibers.

A simple electrostatic model can explain the effect of pH upon the force-pCa relation of skinned frog skeletal muscle fibers.
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一个简单的静电模型可以解释 pH 值对去皮青蛙骨骼肌纤维的力-pCa 关系的影响。

DOI:
10.1016/s0006-3495(81)84797-2
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发表时间:
1981
影响因子:
3.4
通讯作者:
Godt,RE
Godt,RE
中科院分区:
生物学3区
文献类型:
--
作者:
Godt,RE

文献摘要

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蛙骨骼肌纤维的相对力-pCa关系由pH的变化沿pCa轴沿着移动。这种移动被解释为H+和Ca 2+之间竞争肌钙蛋白上的结合位点。不幸的是,结合研究无法证实这种竞争。然而,替代地,数据拟合模型,其中H+影响细丝表面上的可电离基团的解离程度,从而改变细丝周围的静电势。根据玻尔兹曼关系,电势的改变反过来会改变肌钙蛋白结合位点附近的Ca 2+浓度。一个简单的模型,基于表面电位和电荷密度之间的Gouy-Chapman关系,提供了一个定量的解释相对力-pCa曲线与pH值的变化,给出了合理的估计的表面电荷密度的细丝。当电离基团产生的电位具有6.1的对数质子电离常数(pKa),类似于组氨酸上的咪唑基团,并且当这些基团的密度接近从细丝蛋白质的氨基酸分析和细丝几何形状估计时,获得最佳拟合。在初步的实验中,去皮青蛙纤维与焦碳酸二乙酯(DEP)在pH 6的反应力-pCa曲线向低钙移动。这在模型中是预期的,因为据报道,pH 6下的DEP与组氨酸咪唑基团特异性反应,并不可逆地降低其pKa,这将增加细丝的净负电荷。
The relative force-pCa relation of skinned frog skeletal muscle fibers is shifted along the pCa axis by changes in pH. This shift has been interpreted as arising from competition between H+ and Ca2+ for a binding site on troponin. Unfortunately, binding studies have been unable to confirm such competition. Alternatively, however, the data fit a model where H+ influences the degree of dissociation of ionizable groups on the surface of the thin filaments, thus altering the electrostatic potential surrounding the filaments. Alterations in the potential will, in turn, change the concentration of Ca2+ near the troponin binding sites in accordance with the Boltzmann relation. A simple model, based upon the Gouy-Chapman relation between surface potential and charge density, provides a quantitative explanation for the shift of the relative force-pCa curve with pH, given a reasonable estimate of the surface charge density on the thin filament. A best fit is obtained when the ionizable groups giving rise to the potential have a log proton ionization constant (pKa) of 6.1, similar to that for the imidazole group on histidine, and when the density of these groups is near that estimated from amino acid analysis of thin filament proteins and from filament geometry. In preliminary experiments, reaction of skinned frog fibers with diethylpyrocarbonate (DEP) at pH 6 shifted the force-pCa curve toward lower Ca2+. This would be expected in the model since DEP at pH 6 is reported to specifically react with histidine imidazole groups and to irreversibly decrease their pKa, which would increase the net negative charge of the filaments.