Na(+)-K+ pump cycle during beta-adrenergic stimulation of adult rat cardiac myocytes.
Na(+)-K+ pump cycle during beta-adrenergic stimulation of adult rat cardiac myocytes.
复制标题
成年大鼠心肌细胞β-肾上腺素能刺激期间的Na()-K泵循环。
DOI：
10.1111/j.1469-7793.1998.527bt.x
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
Stimers,JR
中科院分区：
文献类型：
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作者：
Dobretsov,M;Hastings,SL;Stimers,JR
1在31~33℃温度下，用全细胞膜片钳技术研究肾上腺素能刺激引起培养的成年大鼠心肌细胞Na+-K+泵电流增加的机制。2在50μ+(0 KI+，20 nM Ca~+，门冬氨酸铯溶液)和5.4MMK+O灌流的心肌细胞中，去甲肾上腺素(NA)和异丙肾上腺素(Iso)(1~50 mMNa)刺激心肌细胞40~45%使其Na~+-K+泵电流增加40~45%。提示肾上腺素能刺激不改变泵部位密度(对照组2 630±370个μm−2和10μm−2 2 540±190个μmNA)。4饱和Na+或K+0(15 0和15~2 0 mM)仍可被NA和Iso刺激。因此，没有迹象表明Na+-K+泵的激活是由Na+i和K+的积累或Na+-K+泵对Na+i和K+o的亲和力的改变所介导的。5Ip和在肾上腺素能刺激下的增加都依赖于[K+]i。当稳态Ip从2.2±0.1 pF−1(P<；0.0 5)下降到1.2±0.1pA时，10μMISO对Ip的刺激从0.38±0.0 4增加到0.67±0.0 6 pF−1(P<；当[K+]i从0增加到100 mm时，Ip-Vm(膜电位)关系呈正斜率([Na+]o，150 mm；[K+]o，5.4 mm)或负斜率([Na+]o，0；[K+]o，0.3 mm)刺激Ip，而Ip-Vm曲线形状不变。因此，肾上腺素对Na+-K+泵的刺激不是由于泵周期的电压依赖步骤的改变。7用Na+-K+泵周期的六步模型模拟这些数据表明，在大鼠心室肌细胞中，来自肾上腺素能受体的信号通过调节泵释放K+的速率来增加Na+-K+泵的速率。
1The mechanisms underlying the increase in Na+‐K+pump current (Ip) caused by adrenergic stimulation were investigated in cultured adult rat cardiac myocytes using the whole‐cell patch‐clamp technique at 31‐33 °C.2In myocytes perfused internally with 50 mmNa+(0 Ki+, 20 nM Ca2+, caesium aspartate solution) and externally with 5.4 mmK+o, noradrenaline (NA) and isoprenaline (Iso) (1‐50 μm) stimulatedIpby 40‐45 %.3Na+‐dependent transientIpmeasurements with 0 mmK+iand 0 mmK+orevealed no change in the total charge transferred by the Na+‐K+pump during the conformational change, suggesting that the pump site density was not changed by adrenergic stimulation (2630 ± 370 pumps μm−2in control and 2540 ± 190 pumps μm−2in the presence of 10 μmNA).4With saturating Na+ior K+o(150 and 15‐20 mm, respectively),Ipwas still stimulated by NA and Iso. Thus, there was no indication that adrenergic activation of the Na+‐K+pump was mediated by accumulation of Na+iand K+oor changes in the Na+‐K+pump affinity for Na+iand K+o.5BothIpand its increase under adrenergic stimulation were found to depend on [K+]i. While steady‐stateIpdecreased from 2.2 ± 0.1 to 1.2 ± 0.1 pA pF−1(P< 0.05), the stimulation ofIpby 10 μmIso increased from 0.38 ± 0.04 to 0.67 ± 0.06 pA pF−1(P< 0.05) with an increase in [K+]ifrom 0 to 100 mm.6Under conditions that cause theIp‐Vm(membrane potential) relationship to express a positive slope ([Na+]o, 150 mm; [K+]o, 5.4 mm) or a negative slope ([Na+]o, 0; [K+]o, 0.3 mm) Iso stimulatedIpwith no change in the shape ofIp‐Vmcurves. Thus, adrenergic stimulation of the Na+‐K+pump was not due to an alteration of voltage‐dependent steps of the pump cycle.7Simulation of these data with a six‐step model of the Na+‐K+pump cycle suggested that in rat ventricular myocytes a signal from adrenergic receptors increased the Na+‐K+pump rate by modulating the rate of K+de‐occlusion and release by the pump.