Harms L, Finta E P, Tschöpl M, Illes P
Department of Pharmacology, University of Freiburg, F.R.G.
Neuroscience. 1992 Jun;48(4):941-52. doi: 10.1016/0306-4522(92)90282-7.
Intracellular recordings were performed in a pontine slice preparation of the rat brain containing the locus coeruleus. The enzymatically stable P2-purinoceptor agonist alpha,beta-methylene ATP increased the firing rate without altering the amplitude or shape of action potentials; the afterhyperpolarization following a spike was not changed either. When locus coeruleus neurons were hyperpolarized by current injection in order to prevent spontaneous firing, alpha,beta-methylene ATP produced depolarization and a slight increase in the apparent input resistance. A combined application of kynurenic acid and bicuculline methiodide failed to alter the alpha,beta-methylene ATP-induced depolarization, and tetrodotoxin only slightly depressed it. A gradual shift of the membrane potential by hyperpolarizing current injection led to a corresponding decrease, but no abolition or reversal of the alpha,beta-methylene ATP effect. In the hyperpolarized region, the current-voltage curve of alpha,beta-methylene ATP came into close approximation with, but did not cross, the control curve. Elevation of the external K+ concentration, or the intracellular application of Cs+ by diffusion from the microelectrode, depressed the response to alpha,beta-methylene ATP; external tetraethylammonium was also inhibitory. External Ba2+ and Cs+ had no effect or only slightly decreased the alpha,beta-methylene ATP-induced depolarization. A low Na+, or a low Ca2+ high Mg2+ medium, as well as the presence of Co2+ in the medium, markedly reduced or even abolished the depolarization by alpha,beta-methylene ATP. ATP itself did not produce consistent changes in the membrane potential or input resistance. However, in the presence of the P1-purinoceptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, ATP consistently increased the firing rate and evoked an inward current. In conclusion, P2-purinoceptor activation appears to depolarize locus coeruleus neurons by inhibiting a persistent potassium current, and at the same time opening calcium-sensitive sodium channels or calcium-sensitive non-selective cationic channels.
在包含蓝斑的大鼠脑桥切片标本上进行细胞内记录。酶稳定的P2嘌呤受体激动剂α,β-亚甲基ATP增加了放电频率，而不改变动作电位的幅度或形状；峰电位后的超极化也没有改变。当通过电流注入使蓝斑神经元超极化以防止自发放电时，α,β-亚甲基ATP产生去极化并使表观输入电阻略有增加。联合应用犬尿氨酸和甲磺酸荷包牡丹碱未能改变α,β-亚甲基ATP诱导的去极化，而河豚毒素仅使其略有降低。通过超极化电流注入使膜电位逐渐偏移导致相应降低，但α,β-亚甲基ATP的效应没有消除或反转。在超极化区域，α,β-亚甲基ATP的电流-电压曲线与对照曲线紧密接近但不相交。升高细胞外K⁺浓度，或通过微电极扩散在细胞内应用Cs⁺，可抑制对α,β-亚甲基ATP的反应；细胞外四乙铵也有抑制作用。细胞外Ba²⁺和Cs⁺没有作用或仅略微降低α,β-亚甲基ATP诱导的去极化。低Na⁺、低Ca²⁺高Mg²⁺培养基以及培养基中存在Co²⁺，可显著降低甚至消除α,β-亚甲基ATP引起的去极化。ATP本身并未在膜电位或输入电阻上产生一致的变化。然而，在存在P1嘌呤受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤的情况下，ATP持续增加放电频率并诱发内向电流。总之，P2嘌呤受体激活似乎通过抑制持续性钾电流使蓝斑神经元去极化，同时开放钙敏感钠通道或钙敏感非选择性阳离子通道。
