二氧化硫衍生物对背根神经元钙通道的影响

应用全细胞膜片钳技术研究了SO₂衍生物对大鼠DRG(背根神经节)神经元不同亚型钙通道的影响. 结果表明,1 μmol/L SO₂衍生物对不同电压下的钙电流均有增大作用,在-10 mV时可使钙电流增幅达到63.4%±5.7%. 在细胞外液中加入不同亚型钙通道的阻滞剂并经过修正计算发现,1 μmol/L SO₂衍生物使L型钙电流增长了82.2%,N型钙电流增长了95.3%,r型(非L型、非N型)钙电流增长了9.4%,说明高阈值激活的N型和L型钙电流对SO₂衍生物特别敏感,推测SO₂衍生物诱发神经性疼痛,引起神经毒性,可能主要通过增大DRG神经元上N型和L型钙通道发生电流介导. 

Effects of SO2 Derivatives on Calcium Channels in DRG Neurons

The effects of SO₂ derivatives on L-type and N-type calcium currents in freshly isolated rat dorsal root ganglion neurons were investigated using the whole-cell configuration of the path-clamp technique. The results showed:first, it was found that 1 μmol/L SO₂ derivatives could increase the amplitudes of calcium currents in a voltage-dependent manner. The average increase of high-voltage-activated calcium currents was 63.4%±5.7% at -10 mV. Second, the sensitivity of SO₂ derivatives on channel subtypes was quantitatively estimated based on the different ratios of L-, N-, r-(non-L- and non-N-types) types expressed in total high-voltage-activated calcium channels when the corresponding selective channel blockers were applied and the calcium currents were recorded. The data showed that 1 μmol/L SO₂ derivatives increased L-type current by 82.2%, increased N-type by 95.3%, and increased residual r type Ca2+ currents by 9.4%, which indicated that both N- and L-type Ca2+ channels were sensitive to SO₂ derivatives. It was suggested that SO₂ derivatives could enhance both types of Ca2+ currents in dorsal root ganglion neurons and then lead to neuropathic pain.