Yusuf I, Yamaoka K, Otsuka H, Yamasaki K, Seyama I
Department of Physiology, Hiroshima University School of Medicine, Japan.
Jpn J Physiol. 1992;42(2):179-91. doi: 10.2170/jjphysiol.42.179.
Pharmacological effects of tyramine and its analogue, N-feruloyl tyramine (NFT), on sodium and calcium currents in frog ventricular myocytes were examined using the whole-cell voltage-clamp technique. To improve the temporal and spatial control of the membrane potential, sodium currents (INa) were recorded in 45.5 mM [Na+]o at 10 degrees C. Both tyramine and NFT (1-100 microM) induced a concentration-dependent decrease in INa evoked from a holding potential of -80 mV without affecting a change in either the time to peak or the time constant for the falling phase of INa. Similarly the reversal potential for INa remained unchanged at a value close to that predicted from the Nernst equation. The finding that both tyramine and NFT decreased INa when activated maximally, from a holding potential of -120 mV, indicates that the amplitude of INa can be reduced independently of a change in the kinetics of the current. In addition, tyramine (100 microM) shifted the membrane potential for half maximal inactivation (Vh) of the steady-state inactivation (h infinity)-curve from -74 to -84 mV without affecting its slope. In contrast, NFT failed to affect the h infinity-curve. The calcium current (ICa) recorded in the presence of 0.3 microM TTX was not affected by either 100 microM tyramine or NFT. We concluded that tyramine directly blocks Na channel by shifting h infinity-curve and by suppressing maximum Na channel conductance, while NFT suppresses only maximum Na channel conductance.
采用全细胞膜片钳技术，研究了酪胺及其类似物N-阿魏酰酪胺（NFT）对蛙心室肌细胞钠电流和钙电流的药理作用。为了改善膜电位的时间和空间控制，在10℃下于45.5 mM [Na⁺]ₒ中记录钠电流（INa）。酪胺和NFT（1 - 100 μM）均使从 - 80 mV的钳制电位诱发的INa呈浓度依赖性降低，而不影响INa峰值时间或下降相的时间常数的变化。同样，INa的反转电位保持不变，其值接近能斯特方程预测的值。当从 - 120 mV的钳制电位最大激活时，酪胺和NFT均降低INa，这一发现表明INa的幅度可独立于电流动力学变化而降低。此外，酪胺（100 μM）使稳态失活（h∞）曲线的半数最大失活膜电位（Vh）从 - 74 mV移至 - 84 mV，而不影响其斜率。相比之下，NFT未能影响h∞曲线。在存在0.3 μM 河豚毒素（TTX）的情况下记录的钙电流（ICa）不受100 μM酪胺或NFT的影响。我们得出结论，酪胺通过移动h∞曲线和抑制最大钠通道电导直接阻断钠通道，而NFT仅抑制最大钠通道电导。
