Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats
Transient voltage-dependent potassium currents are reduced in NTS neurons isolated from renal wrap hypertensive rats
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DOI：
10.1152/jn.00573.2005
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发表时间：
2005-12-01
影响因子：
2.5
通讯作者：
Mifflin, S
中科院分区：
文献类型：
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作者：
Belugin, S;Mifflin, S
采用全细胞膜片钳技术，观察单侧肾切除/肾包裹4周后高血压（HT）大鼠孤束核（NTS）神经元电压依赖性钾通道的变化。一些大鼠在实验前将荧光示踪剂DiA应用于主动脉神经，以识别接受单突触压力感受器传入输入的NTS神经元。4周HT大鼠的平均动脉压（MAP）（165 ± 5 mmHg，n = 26，P < 0.001）高于正常血压（NT）大鼠（69只大鼠中有10只测得109 ± 3 mmHg）。在NT和HT大鼠的NTS神经元中观察到67-82%的瞬时外向电流（TOC）。在激活电压为-10 ~+10 mV时，HT神经元的TOC值显著低于NT神经元（P < 0.001）。电压依赖性激活动力学，稳态失活的电压依赖性，和TOC的上升和衰减时间常数比较NT和HT大鼠分离的神经元没有差异。与NT大鼠相比，HT大鼠神经元TOC的4-氨基吡啶敏感成分显著减少（P < 0.001），而稳态外向电流，无论是否对4-氨基吡啶或四乙基铵敏感，都没有差异。在电流钳下研究，在NT和HT大鼠的60-80%的NTS神经元中观察到延迟兴奋，并且与NT和HT大鼠的神经元相比没有差异。然而，检查显示体细胞DiA荧光的NTS神经元的子集显示，来自HT大鼠的DiA标记的神经元具有比来自NT大鼠的DiA标记的神经元（n = 7个细胞）显著更短的延迟兴奋持续时间（n = 8个细胞，P = 0.022）。HT大鼠延迟兴奋神经元的第一动作电位（AP）较NT大鼠延迟兴奋神经元明显增宽（P = 0.016），复极最大下行速度较NT大鼠延迟兴奋神经元明显减慢（P = 0.014）。在第一个200 ms的持续去极化的AP的数量是HT比NT神经元（P = 0.012）。这些结果表明，HT的4周的持续时间减少在NTS神经元的TOC，这有助于减少延迟兴奋和增加AP反应去极化输入。这些变化可能改变高血压患者的压力反射功能。
Whole cell patch-clamp measurements were made in neurons enzymatically dispersed from the nucleus of the solitary tract (NTS) to determine if alterations occur in voltage-dependent potassium channels from rats made hypertensive (HT) by unilateral nephrectomy/renal wrap for 4 wk. Some rats had the fluorescent tracer DiA applied to the aortic nerve before the experiment to identify NTS neurons receiving monosynaptic baroreceptor afferent inputs. Mean arterial pressure (MAP) was greater in 4-wk HT (165 +/- 5 mmHg, n = 26, P < 0.001) rats compared with normotensive (NT) rats (109 +/- 3 mmHg measured in 10 of 69 rats). Transient outward currents (TOCs) were observed in 67-82% of NTS neurons from NT and HT rats. At activation voltages from -10 to +10 mV, TOCs were significantly less in HT neurons compared with those observed in NT neurons (P < 0.001). There were no differences in the voltage-dependent activation kinetics, the voltage dependence of steady-state inactivation, and the rise and decay time constants of the TOCs comparing neurons isolated from NT and HT rats. The 4-aminopyridine -sensitive component of the TOC was significantly less in neurons from HT compared with NT rats (P < 0.001), whereas steady-state outward currents, whether or not sensitive to 4-aminopyridine or tetraethylammonium, were not different. Delayed excitation, studied under current clamp, was observed in 60-80% of NTS neurons from NT and HT rats and was not different comparing neurons from NT and HT rats. However, examination of the subset of NTS neurons exhibiting somatic DiA fluorescence revealed that DiA-labeled neurons from HT rats had a significantly shorter duration delayed excitation (n = 8 cells, P = 0.022) than DiA-labeled neurons from NT rats (n = 7 cells). Neurons with delayed excitation from HT rats had a significantly broader first action potential (AP) and a slower maximal downstroke velocity of repolarization compared with NT neurons with delayed excitation (P = 0.016 and P = 0.014, respectively). The number of APs in the first 200 ms of a sustained depolarization was greater in HT than NT neurons (P = 0.012). These results suggest that HT of 4-wk duration reduces TOCs in NTS neurons, and this contributes to reduced delayed excitation and increased AP responses to depolarizing inputs. Such changes could alter baroreflex function in hypertension.