Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential.

Positive chronotropic actions of parathyroid hormone and parathyroid hormone-related peptide are associated with increases in the current, I(f), and the slope of the pacemaker potential.
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甲状旁腺激素和甲状旁腺激素相关肽的正变时作用与电流、I(f) 和起搏器电位斜率的增加有关。

DOI:
10.1161/01.cir.96.10.3704
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发表时间:
1997
期刊:
影响因子:
37.8
通讯作者:
Rosen,MR
Rosen,MR
中科院分区:
医学1区
文献类型:
--
作者:
Hara,M;Liu,YM;Zhen,L;Cohen,IS;Yu,H;DaniloJr,P;Ogino,K;Bilezikian,JP;Rosen,MR

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经典的促钙激素甲状旁腺激素(PTH)及其旁分泌因子甲状旁腺激素相关蛋白(PTHrP)均可增加心率。方法与结果采用标准电生理技术研究PTH和PTHrP对兔离体窦房结、犬浦肯野纤维和兔窦房结肌细胞的影响。PTH和PTHrP对窦房结最大舒张电位、激活电压和振幅均无影响(P < 0.05)。PTH和PTHrP≥10 nmol/L时,第4期斜率和自动速率增加(P< 0.05)。在犬浦肯野纤维中也看到了类似的结果。然后我们使用穿孔贴片技术来研究窦房结的ifpacemaker电流。PTH 12.5 nmol/L和PTHrP 12.5 ~ 18 nmol/L分别使fat - 65 mV增加68±41% (n=5)和69±50% (n=5)。两种药物的作用都是可逆的。ifi的增加似乎是由于最大电导的变化,而不是激活的电压依赖性的变化。结论首次为PTH和PTHrP的变时作用提供了直接的电生理支持。他们认为,经典的激素和旁分泌因子可能具有多种功能,在甲状旁腺激素和甲状旁腺thrp的情况下,一种新认识的作用是直接改变自动性。
BackgroundThe classic calciotropic hormone parathyroid hormone (PTH) and its paracrine factor parathyroid hormone–related protein (PTHrP) both increase heart rate.Methods and ResultsWe used standard electrophysiological techniques to study the effects of PTH and PTHrP on isolated rabbit sinus node, isolated canine Purkinje fibers, and disaggregated rabbit sinus node myocytes. Sinus node maximum diastolic potential, activation voltage, and amplitude were unchanged by PTH or PTHrP (P>.05). However, the slope of phase 4 and the automatic rate were increased at PTH and PTHrP ≥10 nmol/L (P<.05). Comparable results were seen in canine Purkinje fibers. We then used the perforated-patch technique to study theIfpacemaker current in sinus node. PTH 12.5 nmol/L and PTHrP 12.5 to 18 nmol/L increasedIfat −65 mV by 68±41% (n=5) and 69±50% (n=5), respectively. Actions of both agents were reversible. The increase inIfappeared to result from a change in maximal conductance and not a shift in the voltage dependence of activation.ConclusionsThese observations provide, for the first time, direct electrophysiological support for the chronotropic actions of PTH and PTHrP. They suggest that classic hormones and paracrine factors can have multiple functions and that in the case of PTH and PTHrP, a newly recognized action is to alter automaticity directly.