Valentijn J A, Valentijn K
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Cell Calcium. 1997 Mar;21(3):241-51. doi: 10.1016/s0143-4160(97)90048-8.
Studies with the Na+ channel blocker tetrodotoxin (TTx) on Ca(2+)-dependent hormone release by mammalian and amphibian pituitary melanotrophs have suggested that the Na+ spikes these cells generate are not responsible for triggering Ca2+ influx and consequently secretion. In contrast, we found in Xenopus laevis melanotrophs that the spontaneously occurring elevations in cytosolic free Ca2+ concentration ("Ca2+ pulses') were dependent on the presence of extracellular Na+ and sensitive to TTx and the Na+ channel activator, veratridine. However, an inhibitory effect of TTx could only be demonstrated when the extracellular Na+ concentration was lowered to near-threshold levels. In voltage-clamp experiments, two distinct Na+ currents were recorded, one sensitive to TTx and the other insensitive to TTx but blocked by micromolar concentrations of Cd2+. Together they appeared to control action potential activity and spontaneous Ca2+ pulsing. These data strongly suggest that Na+ action potentials do regulate cytosolic free Ca2+ concentration in melanotrophs.
使用钠通道阻滞剂河豚毒素（TTx）对哺乳动物和两栖动物垂体黑素细胞钙依赖性激素释放进行的研究表明，这些细胞产生的钠峰电位并非引发钙离子内流进而导致分泌的原因。相比之下，我们在非洲爪蟾黑素细胞中发现，胞质游离钙离子浓度的自发升高（“钙脉冲”）依赖于细胞外钠离子的存在，并且对TTx和钠通道激活剂藜芦碱敏感。然而，只有当细胞外钠离子浓度降低至接近阈值水平时，才能证明TTx具有抑制作用。在电压钳实验中，记录到两种不同的钠电流，一种对TTx敏感，另一种对TTx不敏感，但被微摩尔浓度的镉离子阻断。它们共同似乎控制着动作电位活动和自发钙脉冲。这些数据有力地表明，钠动作电位确实调节黑素细胞中的胞质游离钙离子浓度。
