Krieger P, Büschges A, el Manira A
Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-171 77 Stockholm, Sweden.
J Neurophysiol. 1999 Apr;81(4):1699-705. doi: 10.1152/jn.1999.81.4.1699.
The pharmacology of calcium channels involved in glutamatergic synaptic transmission from reticulospinal axons in the lamprey spinal cord was analyzed with specific agonists and antagonists of different high-voltage activated calcium channels. The N-type calcium channel blocker omega-conotoxin GVIA (omega-CgTx) induced a large decrease of the amplitude of reticulospinal-evoked excitatory postsynaptic potentials (EPSPs). The P/Q-type calcium channel blocker omega-agatoxin IVA (omega-Aga) also reduced the amplitude of the reticulospinal EPSPs, but to a lesser extent than omega-CgTx. The dihydropyridine agonist Bay K and antagonist nimodipine had no effect on the amplitude of the reticulospinal EPSP. Combined application of omega-CgTx and omega-Aga strongly decreased the amplitude the EPSPs but was never able to completely block them, indicating that calcium channels insensitive to these toxins (R-type) are also involved in synaptic transmission from reticulospinal axons. We have previously shown that the group III metabotropic glutamate receptor agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) mediates presynaptic inhibition at the reticulospinal synapse. To test if this presynaptic effect is mediated through inhibition of calcium influx, the effect of L-AP4 on reticulospinal transmission was tested before and after blockade of N-type channels, which contribute predominantly to transmitter release at this synapse. Blocking the N-type channels with omega-CgTx did not prevent inhibition of reticulospinal synaptic transmission by L-AP4. In addition, L-AP4 had no affect on the calcium current recorded in the somata of reticulospinal neurons or on the calcium component of action potentials in reticulospinal axons. These results show that synaptic transmission from reticulospinal axons in the lamprey is mediated by calcium influx through N-, P/Q- and R-type channels, with N-type channels playing the major role. Furthermore, presynaptic inhibition of reticulospinal transmission by L-AP4 appears not to be mediated through inhibition of presynaptic calcium channels.
利用不同高电压激活钙通道的特异性激动剂和拮抗剂，分析了七鳃鳗脊髓中参与网状脊髓轴突谷氨酸能突触传递的钙通道药理学特性。N型钙通道阻滞剂ω-芋螺毒素GVIA（ω-CgTx）可使网状脊髓诱发的兴奋性突触后电位（EPSP）幅度大幅降低。P/Q型钙通道阻滞剂ω-阿加毒素IVA（ω-Aga）也能降低网状脊髓EPSP的幅度，但程度小于ω-CgTx。二氢吡啶激动剂Bay K和拮抗剂尼莫地平对网状脊髓EPSP的幅度无影响。联合应用ω-CgTx和ω-Aga可强烈降低EPSP的幅度，但从未能够完全阻断它们，这表明对这些毒素不敏感的钙通道（R型）也参与网状脊髓轴突的突触传递。我们之前已经表明，III组代谢型谷氨酸受体激动剂L(+)-2-氨基-4-膦酸丁酸（L-AP4）介导网状脊髓突触的突触前抑制。为了测试这种突触前效应是否通过抑制钙内流介导，在阻断主要促成该突触递质释放的N型通道之前和之后，测试了L-AP4对网状脊髓传递的影响。用ω-CgTx阻断N型通道并不能阻止L-AP4对网状脊髓突触传递的抑制作用。此外，L-AP4对网状脊髓神经元胞体中记录的钙电流或网状脊髓轴突动作电位的钙成分没有影响。这些结果表明，七鳃鳗网状脊髓轴突的突触传递是由通过N型、P/Q型和R型通道的钙内流介导的，其中N型通道起主要作用。此外，L-AP4对网状脊髓传递的突触前抑制似乎不是通过抑制突触前钙通道介导的。
