Basal responses of the L-type Ca2+ and hyperpolarization-activated currents to autonomic agonists in the rabbit sino-atrial node
Basal responses of the L-type Ca2+ and hyperpolarization-activated currents to autonomic agonists in the rabbit sino-atrial node
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DOI：
10.1113/jphysiol.1996.sp021220
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发表时间：
1996-03-01
影响因子：
5.5
通讯作者：
DiFrancesco, D
中科院分区：
文献类型：
--
作者：
Zaza, A;Robinson, RB;DiFrancesco, D
1.测定了胆碱能激动剂乙酰胆碱(ACh)和β-肾上腺素能激动剂异丙肾上腺素(Iso)对兔窦房结单个细胞的超极化激活电流(I-f)和L钙电流(I-Ca，I-L)的剂量依赖性。ACh通过使激活曲线负移而抑制I-f，最大作用为-9.9mV，半峰作用在0.019 mU·ACh。高浓度ACh对i-Ca有抑制作用，i-L仅有部分抑制作用(300mM时抑制率为31%)。相比之下，I-f和I-Ca、I-L对Iso的反应剂量范围相似，其半最大增强浓度分别为0.0136和0.0070 mU M。研究了ACh(0.001~0.03mU M)和Iso(0.001~1mM)对自发活动的影响。ACh在与抑制I-f相似的浓度下使舒张期去极化的斜率减小(0.03mM时为50%)。在与影响i-f和i-Ca的浓度相似的浓度下，ISO增强舒张期去极化，i-L(在0.027 mM时半最大效应)5.在模拟舒张期去极化的斜坡钳制方案中，内向硝苯地平敏感电流的激活阈值为-41.22+/-0.68 mV。虽然提高了I-Ca、I-L，但Iso不影响这一阈值。抑制自律性的ACh半峰浓度与I-f相似，均低于调制I-Ca的阈值浓度I-L，这与I-Ca、I-L在M胆碱直接调制起搏中的作用不符。相反，I-f、I-Ca、I-L和自律性的调制发生在相似的Iso浓度。最大舒张期电位(-61.95+/-0.93 mV)与等刺激的钙电流阈值I-L(-39.54+/-1.03 mV)之间的差异表明，该电流仅在舒张期去极化的后期起作用。
1. The dose dependence of the cholinergic agonist acetylcholine (ACh) and the beta-adrenergic agonist isoprenaline (Iso) were determined for the hyperpolarization-activated current (I-f) and the L-type Ca2+ current (I-Ca,I-L) in single cells isolated from the rabbit sino-atrial (SA) node.2. ACh inhibited I-f by a negative shift of its activation curve with a maximal effect of - 9.9 mV; half-maximal effect was produced by 0.019 mu M. ACh. High ACh concentrations were required to inhibit I-Ca,I-L only partially (31% inhibition at 300 mu M).3. In contrast, I-f and I-Ca,I-L responded to Iso over a similar dose range, with concentrations for half-maximal enhancement of 0.0136 and 0.0070 mu M, respectively.4. The effects on spontaneous activity of ACh (range 0.001-0.03 mu M) and Iso (range 0.001-1 mu M) were investigated. ACh decreased the slope of diastolic depolarization at concentrations similar to those inhibiting I-f (> 50% at 0.03 mu M). Iso enhanced diastolic depolarization at concentrations similar to those affecting both I-f and I-Ca,I-L (half-maximal effect at 0.027 mu M)5. In a ramp-clamp protocol simulating diastolic depolarization, the threshold for activation of inward nifedipine-sensitive current was - 41.22 +/- 0.68 mV. Although enhancing I-Ca,I-L, Iso did not affect this threshold.6. Half-maximal ACh h concentrations for inhibition of automaticity and I-f are similar and are lower than the threshold concentrations for modulation of I-Ca,I-L; this argues against a role of I-Ca,I-L in direct muscarinic modulation of pacemaking. In contrast, modulation of I-f, I-Ca,I-L and automaticity occur at similar Iso concentrations. The difference between maximum diastolic potential (- 61.95 +/- 0.93 mV) and the threshold for Iso-stimulated I-Ca,I-L (- 39.54 +/- 1.03 mV) suggests that this current plays a role only at later stages of diastolic depolarization.