Hals G D, Stein P G, Palade P T
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
J Gen Physiol. 1989 Mar;93(3):385-410. doi: 10.1085/jgp.93.3.385.
Previously undescribed high conductance single anion channels from frog skeletal muscle sarcoplasmic reticulum (SR) were studied in native membrane using the "sarcoball" technique (Stein and Palade, 1988). Excised inside-out patches recorded in symmetrical 200 mM TrisCl show the conductance of the channel's predominant state was 505 +/- 25 pS (n = 35). From reversal potentials, the Pcl/PK ratio was 45. The slope conductance vs. Cl- ion concentration curve saturates at 617 pS, with K0.5 estimated at 77 mM. The steady-state open probability (Po) vs. holding potential relationship produces a bell-shaped curve, with Po values reaching a maximum near 1.0 at 0 mV, and falling off to 0.05 at +/- 25 mV. Kinetic analysis of the voltage dependence reveals that while open time constants are decreased somewhat by increases in potential, the largest effect is an increase in long closed times. Despite the channel's high conductance, it maintains a moderate selectivity for smaller anions, but will not pass larger anions such as gluconate, as determined by reversal-potential shifts. At least two substates different from the main open level are distinguishable. These properties are unlike those described for mitochondrial voltage-dependent anion channels or skeletal muscle surface membrane Cl channels and since SR Ca channels are present in equally high density in sarcoball patches, we propose these sarcoball anion channels originate from the SR. Preliminary experiments recording currents from frog SR anion channels fused into liposomes indicate that either biochemical isolation and/or alterations in lipid environment greatly decrease the channel's voltage sensitivity. These results help underline the potential significance of using sarcoballs to study SR channels. The steep voltage sensitivity of the sarcoball anion channel suggests that it could be more actively involved in the regulation of Ca2+ transport by the SR.
我们使用“肌球”技术(Stein和Palade,1988)在天然膜中研究了蛙骨骼肌肌浆网(SR)中以前未描述的高电导单阴离子通道。在对称的200 mM TrisCl中记录的内翻膜片显示,通道主要状态的电导为505±25 pS(n = 35)。根据反转电位,Pcl/PK比值为45。斜率电导与Cl-离子浓度曲线在617 pS处饱和,K0.5估计为77 mM。稳态开放概率(Po)与保持电位的关系产生一条钟形曲线,Po值在0 mV时接近1.0达到最大值,在±25 mV时降至0.05。电压依赖性的动力学分析表明,虽然开放时间常数会随着电位的增加而略有降低,但最大的影响是长关闭时间的增加。尽管该通道具有高电导,但它对较小的阴离子保持适度的选择性,并且如反转电位偏移所确定的那样,不会通过较大的阴离子,如葡萄糖酸盐。至少有两个不同于主要开放水平的亚状态是可区分的。这些特性与线粒体电压依赖性阴离子通道或骨骼肌表面膜Cl通道所描述的特性不同,并且由于SR Ca通道在肌球膜片中同样高密度存在,我们提出这些肌球阴离子通道起源于SR。从融合到脂质体中的蛙SR阴离子通道记录电流的初步实验表明,生化分离和/或脂质环境的改变会大大降低通道的电压敏感性。这些结果有助于强调使用肌球研究SR通道的潜在意义。肌球阴离子通道的陡峭电压敏感性表明它可能更积极地参与SR对Ca2+转运的调节。