The peptide CGRP increases a high-threshold Ca2+ current in rat nodose neurones via a pertussis toxin-sensitive pathway.
The peptide CGRP increases a high-threshold Ca2+ current in rat nodose neurones via a pertussis toxin-sensitive pathway.
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肽 CGRP 通过百日咳毒素敏感途径增加大鼠结状神经元中的高阈值 Ca2 电流。
DOI：
10.1113/jphysiol.1992.sp019306
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
MacDonald,RL
中科院分区：
文献类型：
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作者：
Wiley,JW;Gross,RA;MacDonald,RL
1.采用全细胞膜片钳技术研究降钙素基因相关肽（CGRP）对急性分离的大鼠结状神经节神经元电压门控钙电流的影响，并确定其作用是否通过鸟嘌呤核苷酸结合（G）蛋白介导。2.结状神经节神经元中存在低阈值和高阈值钙电流成分。CGRP对孤立的低阈值电流分量没有影响。然而，CGRP（1 - 1000 nM，ED 50 = 50 nM）引起高阈值钙电流的浓度依赖性增加。CGRP（1 μ M）使这些钙电流的峰值比对照组增加21 +/-4%。3. CGRP增强了-80 mV保持电位诱发的瞬时高阈值钙电流，但不影响-40 mV诱发的缓慢失活高阈值电流。在感觉神经元中已经报道了多种高阈值钙电流。我们不能明确指出CGRP增强了哪种高阈值钙电流成分。然而，基于CGRP增加瞬时但不是缓慢失活的高阈值钙电流的观察结果，我们认为肽主要增强N型钙电流组分。4. CGRP增加了最大峰值电流，并在6个神经元中的3个中引起电流-电压（I-V）关系峰值的适度负移<或= 10 mV。在其余三个神经元中，肽增加了最大峰电流，而没有检测到I-V关系峰的偏移。5.为了确定CGRP诱导的钙电流增强是否与钙电导增加相关，我们研究了当在+30 mV的钳位电位（Vc）下诱发电流时，肽对瞬时电流-电压（I-V）关系的影响，该电压与观察到的最大电流呈正相关（Vc = 0至+10 mV）。CGRP使最大电导增加23 +/-4%。6. CGRP对钙电流的增强不是由于钙通道稳态失活的电压依赖性的变化。在相同的Vc（+10 mV）下，用不同的保持电位（Vh）诱发电流，评价CGRP对钙电流的刺激作用。CGRP诱导的钙电流增加在-60 mV至-110 mV的（Vh）范围内相似，表明该肽不会改变电压依赖性稳态失活。（400字处截断摘要）
1. The whole‐cell variation of the patch clamp technique was used to study the effect of calcitonin gene‐related peptide (CGRP) on voltage‐gated calcium currents in acutely dissociated rat nodose ganglion neurones and to determine if its effects were mediated via a guanine nucleotide binding (G) protein. 2. Both low‐ and high‐threshold calcium current components were present in nodose ganglion neurones. CGRP had no effect on the isolated low‐threshold current component. However, CGRP (1‐1000 nM, ED50 = 50 nM) caused a concentration‐dependent increase in high‐threshold calcium currents. CGRP (1 microM) increased the peak of these calcium currents 21 +/‐ 4% over controls. 3. CGRP enhanced a transient high‐threshold calcium current evoked from a holding potential of ‐80 mV but did not affect the slowly inactivating high‐threshold current evoked from ‐40 mV. Multiple high‐threshold calcium currents have been reported in sensory neurones. We cannot state unequivocally which high‐threshold calcium current component was enhanced by CGRP. However, based on the observation that CGRP increased a transient but not the slowly inactivating high‐threshold calcium current, we believe the peptide enhanced primarily the N‐type calcium current component. 4. CGRP increased the maximal peak current and caused a modest negative shift of < or = 10 mV in the peak of the current‐voltage (I‐V) relation in three of six neurones. In the remaining three neurones the peptide increased the maximal peak current without a detectable shift in the peak of the I‐V relation. 5. To determine if the CGRP‐induced enhancement in calcium current was associated with an increase in calcium conductance, we studied the effect of the peptide on the instantaneous current‐voltage (I‐V) relation when currents were evoked at a clamp potential (Vc) of +30 mV, positive to the observed maximal current (Vc = 0 to +10 mV). CGRP increased the maximal conductance 23 +/‐ 4%. 6. The enhancement of calcium current by CGRP was not due to a shift in the voltage dependency of steady‐state inactivation of the calcium channels. The stimulatory effect of CGRP on calcium current was evaluated by evoking currents from different holding potentials (Vh) at the same Vc (+10 mV). CGRP‐induced increases in calcium currents were similar over the range of (Vh) from ‐60 to ‐110 mV, suggesting that the peptide did not alter voltage‐dependent steady‐state inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)