Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons
Modulation of Ca2+ channel currents of acutely dissociated rat periaqueductal grey neurons
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DOI：
10.1111/j.1469-7793.1998.047bo.x
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发表时间：
1998-05-15
影响因子：
5.5
通讯作者：
Christie, MJ
中科院分区：
文献类型：
--
作者：
Connor, M;Christie, MJ
1.采用全细胞膜片钳技术，观察神经肽伤害素对急性分离的大鼠中脑导水管周围灰质(PAG)神经元钙通道电流(I-BA)的作用。这些作用与阿片受体激动剂和GABA(B)受体激动剂巴氯芬进行了比较。年轻成年大鼠(23-58日龄)的神经元主要表达Omega-conooxoxGVIA(N型)和Omega-agatoxin IVA(P/Q型)敏感的I-ba，以及少量的尼莫地平敏感电流和对所有三种阻断剂的电流抵抗。雌性大鼠神经元中的N型I-BA比例较多，雄性大鼠神经元中的阻性电流比例较多。伤害素(EC50，5 nM)和巴氯芬(EC50，0.8mM)抑制所有PAG神经元的i-ba，而阿片激动剂甲硫氨酸脑啡肽(Met-enkephalin，300 nM-10mU)抑制40%的神经元的i-ba。Met-脑啡肽的作用可被Mu-阿片拮抗剂CTAP逆转，并被Mu-阿片激动剂DAMGO(300 NM-3MU)所模拟。S阿片激动剂DPDPE和Deltorphin II以及IC阿片激动剂U69593不影响任何神经元的i-ba。伤害素的作用不能被阿片拮抗剂纳洛酮或伤害素类似物[desPhe(1)]-伤害素所模仿或阻断。用百日咳毒素(500 ng·ml~(-1))预处理神经元8h，可阻断伤害素和巴氯芬对i-ba的影响。伤害素主要抑制N型(EC50，2 nM，最大抑制50%)和P/Q型(EC50，7 nM；最大抑制，33%)I-ba，而对L型和R型I-ba几乎没有影响。这些结果与前面描述的毒烟切片中伤害素、巴氯芬和类阿片的作用是一致的，即它们与内向整流K+电导的增加相耦合。因此，这些激动剂有可能通过一些不同的细胞效应器来调节FAG神经元的功能。
1. The actions of the neuropeptide nociceptin on the calcium channel currents (I-Ba) of acutely dissociated rat periaqueductal grey (PAG) neurons were examined using whole-cell patch clamp techniques. These effects were compared with those of opioid receptor agonists and the GABA(B) receptor agonist baclofen.2. Neurons from young adult rats (23 to 58 days old) expressed predominantly omega-conotoxin GVIA (N-type)- and omega-agatoxin IVA (P/Q-type)-sensitive I-Ba, together with smaller amounts of nimodipine-sensitive current and current resistant to all three blockers. There was proportionately more N-type I-Ba in neurons from female rats and proportionately more resistant current in neurons from male rats.3. Nociceptin (EC50, 5 nM) and baclofen (EC50, 0.8 mu M) inhibited I-Ba in all PAG neurons, while the opioid agonist methionine enkephalin (met-enkephalin; 300 nM-10 mu M) inhibited I-Ba in 40% of neurons. The effects of met-enkephalin were reversed by the mu-opioid antagonist CTAP, and mimicked by the mu-opioid agonist DAMGO (300 nM-3 mu M). The S-opioid agonists DPDPE and deltorphin II, and the Ic-opioid agonist U69593, did not affect I-Ba in any neuron. The actions of nociceptin were not mimicked or blocked by the opioid antagonist naloxone or the nociceptin analogue [desPhe(1)]-nociceptin.4. The effects of nociceptin and baclofen on I-Ba were blocked by pretreatment of the neurons with pertussis toxin (500 ng ml(-1) 8 h).5. Nociceptin predominantly inhibited the N-type (EC50, 2 nM; maximum inhibition, 50%) and P/Q-type (EC50, 7 nM; maximum inhibition, 33 %) I-Ba while having little effect on the L-type and R-type I-Ba.6. These results are consistent with the previously described actions of nociceptin, baclofen and mu-opioids in FAG slices, whereby they couple to increases in an inwardly rectifying K+ conductance. These agonists thus have the potential to modulate the function of FAG neurons via a number of different cellular effecters.