Burt J M, Spray D C
Department of Physiology, University of Arizona, Tucson 85724.
Circ Res. 1989 Sep;65(3):829-37. doi: 10.1161/01.res.65.3.829.
The effects of halothane and ethrane on gap junction-mediated intercellular communication and on membrane excitability were examined in cultured neonatal rat cardiac myocytes using whole-cell voltage-clamp and current-clamp techniques. Excitability was maintained at doses of both anesthetics that reversibly abolished current flow through junctional membranes. The degree of reduction of junctional conductance was a steep function of the dose of anesthetic; complete block occurred at lower aqueous concentrations of halothane than ethrane. The time course for loss of communication was rapid; 90% reduction of initial junctional conductance occurred in less than 15 seconds after exposure to 2 mM halothane or 4 mM ethrane. Recovery of junctional conductance and junctional permeability to intracellularly injected Lucifer yellow was rapid and complete on washout of the anesthetics. As junctional conductance was reduced by halothane or ethrane exposure, unitary conductance of the gap junctional channels remained constant at about 50 pS. Uncoupling by these anesthetics is thus attributable to a decrease in the number of conducting channels rather than to reduction of the channel's unitary conductance. The data are discussed with regard to the possible role of this intercellular communication pathway in the arrhythmias and alterations of conduction velocity and contractility produced by volatile anesthetics.
运用全细胞膜片钳和电流钳技术，在培养的新生大鼠心肌细胞中检测了氟烷和恩氟烷对缝隙连接介导的细胞间通讯以及膜兴奋性的影响。在两种麻醉剂的剂量下，兴奋性得以维持，而这些剂量可逆地消除了通过连接膜的电流。连接电导的降低程度是麻醉剂剂量的陡峭函数；与恩氟烷相比，在较低的氟烷水溶液浓度下就出现了完全阻断。通讯丧失的时间进程很快；暴露于2 mM氟烷或4 mM恩氟烷后不到15秒，初始连接电导就降低了90%。麻醉剂洗脱后，连接电导和对细胞内注射荧光黄的连接通透性迅速且完全恢复。随着氟烷或恩氟烷暴露导致连接电导降低，缝隙连接通道的单通道电导保持恒定，约为50 pS。因此，这些麻醉剂导致的解偶联归因于传导通道数量的减少，而非通道单通道电导的降低。结合挥发性麻醉剂导致的心律失常、传导速度改变和收缩性改变，讨论了这种细胞间通讯途径可能发挥的作用。
