Nakaya H, Hattori Y, Tohse N, Shida S, Kanno M
Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Pflugers Arch. 1990 Oct;417(2):185-93. doi: 10.1007/BF00370698.
Effects of beta-adrenergic stimulation on the membrane potential and intracellular Na+, K+ and Cl- activities were examined in isolated guinea-pig ventricular muscles using conventional and ion-selective electrodes. Isoproterenol in concentrations of 30 nM - 1 microM produced a transient depolarization followed by a slight hyperpolarization in electrically stimulated or quiescent papillary muscles. The negative logarithm of the concentration producing 50% maximum effect (pD2) for the membrane-depolarizing effect of isoproterenol was smaller than that for the positive inotropic effect, suggesting that a higher level of cAMP accumulation is required to produce the transient depolarization. Whereas the isoproterenol(1 microM)-induced depolarization was not blocked by tetrodotoxin (10 microM), nifedipine (10 microM), Cs+ (5 mM), Ba2+ (0.3 mM), amiloride (1 mM) or ouabain (10 microM), it was significantly attenuated by anthracene-9-carboxylic acid (1 mM), a Cl(-)-channel blocker. Intracellular K+ activity increased, whereas intracellular Na+ activity slightly decreased during the transient depolarization. Intracellular Cl- activity significantly decreased during the isoproterenol-induced depolarization of the resting membrane. These results suggest that an inward current resulting from outward Cl- movement, rather than inward Na+ movement, may be involved in the beta-adrenoceptor-mediated membrane depolarization.
使用传统电极和离子选择性电极，在分离的豚鼠心室肌中研究了β-肾上腺素能刺激对膜电位以及细胞内Na⁺、K⁺和Cl⁻活性的影响。浓度为30 nM - 1 μM的异丙肾上腺素在电刺激或静息的乳头肌中产生短暂的去极化，随后是轻微的超极化。异丙肾上腺素膜去极化作用产生50%最大效应时的浓度的负对数（pD2）小于其正性肌力作用的pD2，这表明产生短暂去极化需要更高水平的cAMP积累。虽然异丙肾上腺素（1 μM）诱导的去极化不受河豚毒素（10 μM）、硝苯地平（10 μM）、Cs⁺（5 mM）、Ba²⁺（0.3 mM）、氨氯吡咪（1 mM）或哇巴因（10 μM）的阻断，但它被Cl⁻通道阻滞剂9-蒽羧酸（1 mM）显著减弱。在短暂去极化期间，细胞内K⁺活性增加，而细胞内Na⁺活性略有下降。在异丙肾上腺素诱导的静息膜去极化过程中，细胞内Cl⁻活性显著降低。这些结果表明，β-肾上腺素能受体介导的膜去极化可能涉及由Cl⁻外流而非Na⁺内流产生的内向电流。
