Alpha-adrenergic modulation of ionic currents in cultured parasympathetic neurons from rat intracardiac ganglia.
Alpha-adrenergic modulation of ionic currents in cultured parasympathetic neurons from rat intracardiac ganglia.
复制标题
大鼠心内神经节培养的副交感神经元中离子电流的α-肾上腺素调节。
DOI：
10.1152/jn.1993.69.4.1060
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发表时间：
1993
影响因子：
2.5
通讯作者：
Adams,DJ
中科院分区：
文献类型：
--
作者：
Xu,ZJ;Adams,DJ
1. 研究了α -肾上腺素能激动剂对培养的大鼠心内神经节副交感神经细胞离子电导的调节作用。在药物阻断Na+和K+电流的情况下，将去甲肾上腺素（NE， 25-100微米）应用于离体神经元的胞体，可可逆地降低由去极化电流引起的Ca（2+）依赖性动作电位的振幅和持续时间。2. 在全细胞电压箝位模式下，NE的应用可逆地降低了Ca2+电流（ICa）的激活幅度和速率。振幅抑制在电流峰值（55%）比在700ms脉冲末端（20%）更大。最大剂量的NE只产生大约60%的ICa峰振幅抑制。3. 在NE不存在的情况下，ICa的失活最适合用两个指数函数的和来描述，而在NE存在的情况下，则用单个指数函数来描述。这些结果表明，NE优先抑制这些副交感神经细胞中Ca2+电流的快速失活成分。4. 在-40至+150 mV的所有电压下，NE通过开放的Ca通道可逆地降低了Ba2+尾电流的幅值，并在尾电流的电流-电压（I-V）关系中确定了激活曲线的轻微移位。NE没有改变钙离子通道稳态失活的电压依赖性。5. 在硝苯地平不存在或不存在的情况下，NE都能抑制Ca2+电流，但在存在omega- concontoxin （omega-CGTX）的情况下，NE的抑制程度较低，这表明NE抑制的Ca通道主要对omega-CGTX敏感。6. NE对ICa的抑制作用可由α - 1肾上腺素能激动剂甲氧沙明和苯肾上腺素模拟，并在α - 2肾上腺素受体拮抗剂育亨宾（10微米）存在时增强。α -肾上腺素能拮抗剂酚妥拉明（1 μ m）可拮抗NE对ICa的抑制，但吡唑嗪（1-10 μ m）、育亨宾或β -肾上腺素能拮抗剂普萘洛尔（1 μ m）不能拮抗NE。综上所述，这些结果表明，NE对大鼠副交感心脏神经元Ca2+电流的抑制是由α -肾上腺素能受体介导的，其特性可能不同于α 1-和α 2-肾上腺素受体。7. 在研究的大约35%的神经元中，NE不仅减少了去极化激活的内向Ca2+电流，而且增加了向外电流，使I-V曲线和反转电位向负电压移动。（摘要删节为400字）
1. Modulation of ionic conductances by alpha-adrenergic agonists was investigated in cultured parasympathetic neurons from rat intracardiac ganglia. Application of norepinephrine (NE, 25-100 microM) to the soma of isolated neurons reversibly reduced both the amplitude and duration of the Ca(2+)-dependent action potential evoked by injection of depolarizing current when Na+ and K+ currents were blocked pharmacologically. 2. In the whole-cell voltage-clamp mode, application of NE reversibly reduced the amplitude and rate of activation of Ca2+ current (ICa). The amplitude inhibition was greater at the peak of the current (55%) than at the end of a 700-ms pulse (20%). Maximal doses of NE produced only approximately 60% inhibition of peak ICa amplitude. 3. Inactivation of ICa was best fit by the sum of two exponential functions in the absence of NE, but was described by a single exponential function in the presence of NE. These results suggest that NE preferentially inhibited a fast inactivating component of the Ca2+ current in these parasympathetic neurons. 4. NE reversibly reduced the amplitude of Ba2+ tail currents through open Ca channels at all voltages from -40 to +150 mV with a slight shift in the activation curve determined from the current-voltage (I-V) relationship for the tail currents. NE did not change the voltage dependence of the steady-state inactivation of the calcium channels. 5. NE inhibited Ca2+ current either in the absence or presence of nifedipine but to a lesser extent in the presence of omega-conotoxin (omega-CGTX), suggesting that the Ca channels inhibited by NE are predominantly omega-CGTX sensitive. 6. The inhibition of ICa by NE was mimicked by the alpha 1-adrenergic agonists methoxamine and phenylephrine and potentiated in the presence of the alpha 2-adrenoceptor antagonist yohimbine (10 microM). NE inhibition of ICa was antagonized by bath application of the alpha-adrenergic antagonist phentolamine (1 microM), but not by prazosin (1-10 microM), yohimbine, or the beta-adrenergic antagonist propranolol (1 microM). Taken together, these results suggest that NE inhibition of Ca2+ current in rat parasympathetic cardiac neurons is mediated by an alpha-adrenergic receptor with properties that may differ from alpha 1- and alpha 2-adrenoceptors. 7. In approximately 35% of neurons studied, NE not only reduced depolarization-activated inward Ca2+ current but also increased an outward current, with a shift of the I-V curve and reversal potential to more negative voltages.(ABSTRACT TRUNCATED AT 400 WORDS)