G protein coupled receptors (GPCRs) play a key role in the vast majority of cellular signal transduction processes. Previous experimental evidence has shown that sodium ion (Na⁺) allosterically modulate several class A GPCRs and theoretical studies suggested that the same also holds true for muscarinic receptors. Here we examined, using Xenopus oocytes as an expression system, the effect of Na⁺ on a prototypical GPCR, the M2 muscarinic receptor (M2R). We found that removal of extracellular Na⁺ resulted in a decrease in the potency of ACh toward the M2R and that a conserved aspartate in transmembrane domain 2 is crucial for this effect. We further show that this allosteric effect of Na⁺ does not underlie the voltage-dependence of this receptor.

G蛋白偶联受体（GPCR）在绝大多数细胞信号转导过程中起着关键作用。先前的实验证据表明，钠离子（Na ⁺）会变构调节几种A类GPCR，理论研究表明，毒蕈碱受体也是如此。在这里，我们使用非洲爪蟾卵母细胞作为表达系统，研究了Na ⁺对原型GPCR M2毒蕈碱受体（M2R）的影响。我们发现去除细胞外Na ⁺导致ACh对M2R的效力降低，跨膜结构域2中保守的天冬氨酸对该作用至关重要。我们进一步证明了Na ^+的这种变构作用 并不构成该受体的电压依赖性。