Strøbaek D, Christophersen P, Dissing S, Olesen S P
NeuroSearch A/S, Smedeland, Glostrup, Denmark.
Am J Physiol. 1996 Nov;271(5 Pt 1):C1463-71. doi: 10.1152/ajpcell.1996.271.5.C1463.
Coronary artery smooth muscle cells express G protein-coupled purinoceptors, and we report here for the first time how receptor activation by extracellular ATP influences cell membrane currents and membrane potential in human cells. ATP (100 microM) stimulated a triphasic change in membrane potential lasting several seconds, which was caused by sequential opening of transient inward and outward conductances. The inward current was carried by Cl- and the outward current by K+, as shown by ion substitution and changes in holding potential. Both currents were independent of the presence of external Ca2+ but were blocked by strong buffering of Ca2+ in the internal solution. The P2u- and P2y-purinoceptor agonists UTP and 2-methylthioadenosine 5'-triphosphate activated similar currents, whereas the P2x-receptor agonist alpha, beta-methyleneadenosine 5'-triphosphate and the P1-receptor agonist adenosine failed to stimulate any whole cell currents. The ATP-activated K+ current was inhibited by iberiotoxin (200 nM), and it was potentiated by the BK channel activator NS-1619 (30 microM). In cell-attached recordings, ATP activated a 230-pS BK channel. In conclusion, ATP acting via P2 purinoceptors stimulated release of Ca2+ from internal stores and transiently activated depolarizing Cl- and hyperpolarizing BK channels in human coronary artery smooth muscle cells.
冠状动脉平滑肌细胞表达G蛋白偶联嘌呤受体，我们在此首次报告细胞外ATP激活受体如何影响人细胞的细胞膜电流和膜电位。ATP（100微摩尔）刺激膜电位发生持续数秒的三相变化，这是由瞬时内向和外向电导的顺序开放引起的。内向电流由Cl-携带，外向电流由K+携带，这通过离子替代和钳制电位的变化得以证明。两种电流均不依赖于细胞外Ca2+的存在，但在细胞内溶液中Ca2+被强力缓冲时会被阻断。P2u和P2y嘌呤受体激动剂UTP和2-甲硫基腺苷5'-三磷酸激活类似电流，而P2x受体激动剂α,β-亚甲基腺苷5'-三磷酸和P1受体激动剂腺苷未能刺激任何全细胞电流。ATP激活的K+电流被iberiotoxin（200纳摩尔）抑制，并被BK通道激活剂NS-1619（30微摩尔）增强。在细胞贴附式记录中，ATP激活了一个230皮秒的BK通道。总之，通过P2嘌呤受体起作用的ATP刺激了细胞内储存的Ca2+释放，并瞬时激活了人冠状动脉平滑肌细胞中的去极化Cl-通道和超极化BK通道。
