Abstract：
Smooth muscle cells (SMCs), Interstitial cells of Cajal (ICC) and Platelet-derived growth factor receptor α positive (PDGFRα+) cells form an integrated, electrical syncytium within the gastrointestinal (GI) muscular tissues known as the SIP syncytium. Immunohistochemical analysis of gastric corpus muscles showed that c-KIT+/ANO1+ ICC-IM and PDGFRα+ cells were closely apposed to one another in the same anatomical niches. We used intracellular microelectrode recording from corpus muscle bundles to characterize the roles of intramuscular ICC and PDGFRα+ cells in conditioning membrane potentials of gastric muscles. In muscle bundles, that have a relatively higher input impedance than larger muscle strips or sheets, we recorded an ongoing discharge of stochastic fluctuations in membrane potential, previously called unitary potentials or spontaneous transient depolarizations (STDs) and spontaneous transient hyperpolarizations (STHs). We reasoned that STDs should be blocked by antagonists of ANO1, the signature conductance of ICC. Activation of ANO1 has been shown to generate spontaneous transient inward currents (STICs), which are the basis for STDs. Ani9 reduced membrane noise and caused hyperpolarization, but this agent did not block the fluctuations in membrane potential quantitatively. Apamin, an antagonist of small conductance Ca2+-activated K+ channels (SK3), the signature conductance in PDGFRα+ cells, further reduced membrane noise and caused depolarization. Reversing the order of channel antagonists reversed the sequence of depolarization and hyperpolarization. These experiments show that the ongoing discharge of STDs and STHs by ICC and PDGFRα+ cells, respectively, exerts conditioning effects on membrane potentials in the SIP syncytium that would effectively regulate the excitability of SMCs.
摘要：
平滑肌细胞（SMC），Cajal间质细胞(ICC)与血小板源性生长因子受体α阳性(PDGFRα+)细胞形成整合,胃肠道（GI）肌肉组织内的电合胞体称为SIP合胞体。胃体肌肉的免疫组织化学分析表明，c-KIT/ANO1ICC-IM和PDGFRα细胞在相同的解剖结构中彼此紧密并列。我们使用来自肌体束的细胞内微电极记录来表征肌内ICC和PDGFRα细胞在调节胃肌膜电位中的作用。在肌肉束中，比较大的肌肉条或肌肉片具有相对较高的输入阻抗，我们记录了膜电位随机波动的持续放电，以前称为单一电位或自发瞬态去极化（STD）和自发瞬态超极化（STH）。我们认为STD应该被ANO1的拮抗剂阻断，ANO1是ICC的特征电导。ANO1的激活已被证明会产生自发的瞬态内向电流（STIC），这是性病的基础。Ani9降低了膜噪声并导致超极化，但是这种试剂不能定量地阻止膜电位的波动。阿帕明,小电导Ca2+激活的K+通道（SK3）的拮抗剂，PDGFRα+细胞中的特征电导，进一步降低膜噪声和引起去极化。逆转通道拮抗剂的顺序可以逆转去极化和超极化的顺序。这些实验表明，ICC和PDGFRα+细胞对STD和STHS的持续放电，分别,对SIP合胞体中的膜电位发挥调节作用，可有效调节SMC的兴奋性。
