Boyden P A, Cranefield P F, Gadsby D C
J Physiol. 1983 Jun;339:185-206. doi: 10.1113/jphysiol.1983.sp014711.
The mechanism of the noradrenaline-induced hyperpolarization was investigated in small strips of coronary sinus tissue mounted in a fast-flow system. The recorded hyperpolarization was negligibly small in response to 10 nM-noradrenaline but was maximal at 10 microM (average amplitude 23 mV, in 4 mM-K solution). The hyperpolarization was unaffected by 1 microM-phentolamine but was abolished by 10 microM-propranolol and so is presumably mediated via beta-adrenoceptors. The noradrenaline-induced hyperpolarization became smaller when the extracellular K concentration ([K]o) was raised or when the extracellular Na concentration was lowered. These results are consistent with two general mechanisms: noradrenaline might cause hyperpolarization by stimulating the Na/K pump to generate more outward current, as previously suggested for other cell types. Alternatively, noradrenaline might lower the permeability ratio, PNa/PK, by reducing the permeability coefficient for Na (PNa) and/or increasing that for K (PK). The noradrenaline-induced hyperpolarization is not diminished during exposure to 5 microM-acetylstrophanthidin, or to K-free solution, or to K-free solution containing acetylstrophanthidin. We conclude that the hyperpolarization does not reflect enhanced electrogenic pump activity. Conductance measurements using two micro-electrodes in very small preparations revealed that, like the muscarinic agonist carbachol, noradrenaline caused an increase in membrane slope conductance. Steady-state current-voltage curves obtained in the presence of noradrenaline, in the presence of carbachol, and in the absence of both drugs all crossed each other at about the same level of membrane potential. During the maintained injection of sufficiently large hyperpolarizing current, application of either noradrenaline or carbachol causes depolarization instead of hyperpolarization. The cross-over or 'reversal' potentials of current-voltage curves, determined with and without the drugs, vary with [K]o approximately as does the K equilibrium potential calculated assuming the intracellular K concentration to be 155 mM. We conclude that, like carbachol and acetylcholine, noradrenaline causes a specific increase in the K permeability of coronary sinus cells.
采用安装在快速流动系统中的冠状窦组织小条来研究去甲肾上腺素诱导超极化的机制。对于10 nM去甲肾上腺素，记录到的超极化极小，但在10 μM时最大（在4 mM - K溶液中平均幅度为23 mV）。该超极化不受1 μM酚妥拉明影响，但被10 μM普萘洛尔消除，因此推测是通过β - 肾上腺素能受体介导的。当细胞外K浓度（[K]o）升高或细胞外Na浓度降低时，去甲肾上腺素诱导的超极化变小。这些结果与两种一般机制一致：去甲肾上腺素可能如先前对其他细胞类型所提出的那样，通过刺激Na / K泵产生更多外向电流来引起超极化。或者，去甲肾上腺素可能通过降低Na的通透系数（PNa）和/或增加K的通透系数（PK）来降低通透率PNa / PK。在暴露于5 μM乙酰毒毛花苷、无K溶液或含乙酰毒毛花苷的无K溶液期间，去甲肾上腺素诱导的超极化并未减弱。我们得出结论，该超极化并不反映增强的生电泵活性。在非常小的标本中使用两个微电极进行的电导测量表明，与毒蕈碱激动剂卡巴胆碱一样，去甲肾上腺素导致膜斜率电导增加。在存在去甲肾上腺素、存在卡巴胆碱以及两种药物都不存在的情况下获得的稳态电流 - 电压曲线在大约相同的膜电位水平相互交叉。在持续注入足够大的超极化电流期间，应用去甲肾上腺素或卡巴胆碱都会导致去极化而非超极化。有药和无药情况下测定的电流 - 电压曲线的交叉或“反转”电位随[K]o变化，大致与假设细胞内K浓度为155 mM计算出的K平衡电位相同。我们得出结论，与卡巴胆碱和乙酰胆碱一样，去甲肾上腺素导致冠状窦细胞的K通透性特异性增加。
