Mak D O, Foskett J K
Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6100, USA.
Am J Physiol. 1998 Jul;275(1):C179-88. doi: 10.1152/ajpcell.1998.275.1.C179.
The effects of Mg2+ and Ba2+ on single-channel properties of the inositol 1,4,5-trisphosphate receptor (IP3R) were studied by patch clamp of isolated nuclei from Xenopus oocytes. In 140 mM K+ the IP3R channel kinetics and presence of conductance substates were similar over a range (0-9.5 mM) of free Mg2+. In 0 mM Mg2+ the channel current-voltage (I-V) relation was linear with conductance of approximately 320 pS. Conductance varied slowly and continuously over a wide range (SD approximately 60 pS) and sometimes fluctuated during single openings. The presence of Mg2+ on either or both sides of the channel reduced the current (blocking constant approximately 0.6 mM in symmetrical Mg2+), as well as the range of conductances observed, and made the I-V relation nonlinear (slope conductance approximately 120 pS near 0 mV and approximately 360 pS at +/-70 mV in symmetrical 2.5 mM Mg2+). Ba2+ exhibited similar effects on channel conductance. Mg2+ and Ba2+ permeated the channel with a ratio of permeability of Ba2+ to Mg2+ to K+ of 3.5:2.6:1. These results indicate that divalent cations induce nonlinearity in the I-V relation and reduce current by a mechanism involving permeation block of the IP3R due to strong binding to site(s) in the conduction pathway. Furthermore, stabilization of conductance by divalent cations reveals a novel interaction between the cations and the IP3R.
通过膜片钳技术研究了Mg2+和Ba2+对非洲爪蟾卵母细胞分离细胞核中肌醇1,4,5 -三磷酸受体（IP3R）单通道特性的影响。在140 mM K+条件下，在0 - 9.5 mM的游离Mg2+范围内，IP3R通道动力学和电导亚态的存在情况相似。在0 mM Mg2+时，通道电流-电压（I-V）关系呈线性，电导约为320 pS。电导在很宽的范围内缓慢且连续变化（标准差约为60 pS），并且在单个开放过程中有时会波动。通道两侧存在Mg2+会降低电流（在对称Mg2+中阻断常数约为0.6 mM），以及观察到的电导范围，并使I-V关系呈非线性（在对称的2.5 mM Mg2+中，接近0 mV时斜率电导约为120 pS，在±70 mV时约为360 pS）。Ba2+对通道电导表现出类似的影响。Mg2+和Ba2+可透过通道，Ba2+、Mg2+与K+的渗透率之比为3.5:2.6:1。这些结果表明，二价阳离子通过一种机制诱导I-V关系的非线性并降低电流，该机制涉及由于与传导途径中的位点强烈结合而对IP3R的通透阻滞。此外，二价阳离子对电导的稳定作用揭示了阳离子与IP3R之间的一种新型相互作用。
