Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes.
Ionic basis for the antagonism between adenosine and isoproterenol on isolated mammalian ventricular myocytes.
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腺苷和异丙肾上腺素对离体哺乳动物心室肌细胞拮抗作用的离子基础。
DOI：
10.1161/01.res.55.3.309
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发表时间：
1984
影响因子：
20.1
通讯作者：
Belardinelli,L
中科院分区：
文献类型：
--
作者：
Isenberg,G;Belardinelli,L
用双微电极电压钳技术研究了腺苷和异丙肾上腺素对牛和豚鼠心室肌细胞膜电流的影响。腺苷(50微米至0.2 mM)对所测膜电流均无影响，但可拮抗10 nM异丙肾上腺素的作用。异丙肾上腺素使钙离子膜电流峰值从对照的4.8+/-0.6 nA增加到8.6+/-0.8 nA，腺苷使其降低到5.7+/-0.7 nA(6个细胞的平均+/-扫描电子显微镜)。单用异丙肾上腺素或异丙肾上腺素+腺苷不改变失活时间常数，也不改变钙离子膜电流峰值的电压依赖性。因此，异丙肾上腺素引起的改变可以描述为最大钙电导从0.86+/-0.7增加到1.55+/-0.04ms/cm2，并被腺苷部分拮抗到0.97+/-0.04ms/cm2。异丙肾上腺素使钙膜电流的非失活成分从17+/-1增加到24+/-4%，腺苷使其减少到18+/-2%(n=4)。稳态激活和失活变量保持不变。与这些对钙膜电流的影响一致，腺苷完全拮抗异丙肾上腺素引起的无钠介质中慢动作电位的增加。异丙肾上腺素在-90 mV和-30 mV之间(即可能的iK1)增加稳态外向电流。腺苷对钾电流无影响，但可拮抗异丙肾上腺素的作用。25 mM钾的慢动作电位可被异丙肾上腺素增强，而腺苷仅适度减弱。因此，在25 mM钾离子中，腺苷不能拮抗异丙肾上腺素引起的膜电流改变。在25 mM的钾离子中，腺苷不能抑制异丙肾上腺素的作用，这种作用不能被长达1分钟的预脉冲处理到-45 mV所模拟。结果表明，腺苷本身(不含异丙肾上腺素)对最大钙电导无影响，腺苷可拮抗异丙肾上腺素引起的环状腺苷3‘，5’-单磷酸增加，从而导致最大钙电导增加，这可能是腺苷减弱异丙肾上腺素刺激作用的原因之一。
We studied the effects of adenosine and isoproterenol on membrane currents of isolated bovine and guinea pig ventricular myocytes with a two-microelectrode voltage clamp technique. Adenosine (50 microM to 0.2 mM) alone had no effect on any of the membrane currents measured, but it antagonized the effects induced by 10 nM isoproterenol. Peak calcium membrane current was augmented by isoproterenol from a control of 4.8 +/- 0.6 to 8.6 +/- 0.8 nA and adenosine reduced it to 5.7 +/- 0.7 nA (mean +/- SEM of six cells). The inactivation time constant was not altered by isoproterenol alone or isoproterenol plus adenosine, and neither was the voltage dependence of peak calcium membrane current. Thus, the changes caused by isoproterenol could be described as an increase in maximal calcium conductance from 0.86 +/- 0.7 to 1.55 +/- 0.04 mS/cm2 and partially antagonized by adenosine to 0.97 +/- 0.04 mS/cm2. Isoproterenol also increased the non-inactivating component of calcium membrane current from 17 +/- 1 to 24 +/- 4%, and adenosine reduced it to 18 +/- 2% (n = 4). The steady state activation and inactivation variables remained unchanged. Consistent with these effects on calcium membrane current, adenosine completely antagonized the isoproterenol-induced increase of the slow action potentials obtained in sodium-free medium. Isoproterenol increased the steady state outward currents at potentials between -90 and -30 mV (i.e., probable iK1). Adenosine alone had no effect on potassium membrane current, but it antagonized the effects of isoproterenol. Slow action potentials in 25 mM potassium were enhanced by isoproterenol, but were only moderately attenuated by adenosine. Accordingly, in 25 mM potassium the isoproterenol-induced changes in membrane currents were not antagonized by adenosine. This lack of inhibition by adenosine of the isoproterenol effects in 25 mM potassium could not be mimicked by 1-minute-long conditioning prepulses to -45 mV. The results indicate that adenosine by itself (absence of isoproterenol) has no effect on maximal calcium conductance, that the isoproterenol-induced increase in cyclic adenosine 3',5'-monophosphate, which leads to an increase in maximal calcium conductance, is antagonized by adenosine, and that such action can account for the ability of adenosine to attenuate the stimulatory effects of isoproterenol.