MacDonell K L, Severson D L, Giles W R
Department of Pharmacology and Therapeutics, Heritage Medical Research Centre, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Am J Physiol. 1998 Dec;275(6):H2291-9. doi: 10.1152/ajpheart.1998.275.6.H2291.
Sphingosine 1-phosphate (S-1-P) is a bioactive sphingolipid that is released from activated platelets. Extracellular S-1-P augments an inwardly rectifying potassium conductance in cultured atrial preparations, but the electrophysiological effects of this compound in the ventricle are unknown. The electrophysiological effects of S-1-P were examined in single myocytes from rat ventricular muscle. Action potential waveforms and underlying ionic currents in the presence and absence of 3 microM S-1-P (1-6 min) were recorded. S-1-P increased the minimum stimulus current needed to elicit an action potential by approximately 100 pA. Pertussis toxin or preexposure to S-1-P did not alter this effect. The action potential waveform was unchanged by S-1-P. The inward sodium current (INa) was examined in a range of membrane potentials just negative to the potential for firing an action potential. S-1-P reversibly inhibited peak INa by approximately 50 pA, whereas the inward rectifier potassium current was not significantly changed. The results of this study suggest that S-1-P inhibits rat ventricular excitability by reducing INa.
1-磷酸鞘氨醇（S-1-P）是一种从活化血小板中释放出来的生物活性鞘脂。细胞外的S-1-P可增强培养心房组织中的内向整流钾电导，但该化合物在心室中的电生理作用尚不清楚。本研究检测了S-1-P对大鼠心室肌单个心肌细胞的电生理作用。记录了存在和不存在3 microM S-1-P（1-6分钟）时的动作电位波形和相关离子电流。S-1-P使引发动作电位所需的最小刺激电流增加了约100 pA。百日咳毒素或预先暴露于S-1-P均未改变这种作用。S-1-P未改变动作电位波形。在略低于引发动作电位电位的一系列膜电位下检测内向钠电流（INa）。S-1-P可逆性地抑制峰值INa约50 pA，而内向整流钾电流无明显变化。本研究结果表明，S-1-P通过降低INa来抑制大鼠心室的兴奋性。
