Increased Excitability of Afferent Neurons Innervating Rat Urinary Bladder after Chronic Bladder Inflammation
Increased Excitability of Afferent Neurons Innervating Rat Urinary Bladder after Chronic Bladder Inflammation
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DOI：
10.1523/jneurosci.19-11-04644.1999
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发表时间：
1999-06
期刊：
影响因子：
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通讯作者：
N. Yoshimura;W. D. de Groat
中科院分区：
文献类型：
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作者：
N. Yoshimura;W. D. de Groat
用环磷酰胺（CTX; 75 mg/kg）诱发大鼠慢性膀胱炎2周后，观察L 6和S1背根神经节内膀胱传入神经元的特性。全细胞膜片钳记录显示，对照组大鼠膀胱传入神经元中70%对辣椒素敏感，其高阈值长时程动作电位不被河豚毒素（TTX; 1 μm）阻断。这些神经元表现出膜电位弛豫引起的去极化电流脉冲和相位发射持续膜去极化过程中的电压响应。经MTX治疗后，相似比例（71%）的膀胱传入神经元对辣椒素敏感，并伴有TTX抗性尖峰。但神经元的直径明显大于对照组（29.6 ± 1.0 μm vs 23.6 ± 0.8 μm）。CYP给药大鼠的TTX抗性膀胱传入神经元表现出较低的尖峰激活阈值（−25.4 ± 0.5 mV），低于对照大鼠的阈值（−21.4 ± 0.9 mV），并且在去极化期间未表现出膜电位松弛。CYP处理大鼠中70%的TTX抗性膀胱传入神经元表现出强直放电（在500 msec去极化脉冲期间平均12.3 ± 1.4个尖峰），而正常膀胱传入神经元中的相位放电（1.2 ± 0.2个尖峰）。4-氨基吡啶（1毫米）的应用程序正常TTX耐膀胱传入神经元模仿的变化，在放电特性后的治疗。经CYP处理的TTX抗性膀胱传入神经元在去极化至0 mV时A型K+电流（IA）的峰值密度（42.9 pA/pF）显著小于对照组（109.4 pA/pF），且经CYP处理后IA电流的失活曲线向更高的超极化水平移动约15 mV。这些数据表明，慢性炎症诱导体肥大，并通过抑制IA通道增加C纤维膀胱传入神经元的兴奋性。感觉通路中类似的电变化可能导致膀胱炎引起的疼痛和膀胱活动过度。
The properties of bladder afferent neurons in L6 and S1 dorsal root ganglia of adult rats were evaluated after chronic bladder inflammation induced by 2 week treatment with cyclophosphamide (CYP; 75 mg/kg). Whole-cell patch-clamp recordings revealed that most (70%) of the dissociated bladder afferent neurons from control rats were capsaicin sensitive, with high-threshold long-duration action potentials that were not blocked by tetrodotoxin (TTX; 1 μm). These neurons exhibited membrane potential relaxations during voltage responses elicited by depolarizing current pulses and phasic firing during sustained membrane depolarization. After CYP treatment, a similar proportion (71%) of bladder afferent neurons were capsaicin sensitive with TTX-resistant spikes. However, the neurons were significantly larger in size (diameter 29.6 ± 1.0 μm vs 23.6 ± 0.8 μm in controls). TTX-resistant bladder afferent neurons from CYP-treated rats exhibited lower thresholds for spike activation (−25.4 ± 0.5 mV) than those from control rats (−21.4 ± 0.9 mV) and did not exhibit membrane potential relaxation during depolarization. Seventy percent of TTX-resistant bladder afferent neurons from CYP-treated rats exhibited tonic firing (average 12.3 ± 1.4 spikes during a 500 msec depolarizing pulse) versus phasic firing (1.2 ± 0.2 spikes) in normal bladder afferent neurons. Application of 4-aminopyridine (1 mm) to normal TTX-resistant bladder afferent neurons mimicked the changes in firing properties after CYP treatment. The peak density of an A-type K+ current (IA) during depolarizations to 0 mV in TTX-resistant bladder afferent neurons from CYP-treated rats was significantly smaller (42.9 pA/pF) than that from control rats (109.4 pA/pF), and the inactivation curve of the IA current was displaced to more hyperpolarized levels by ∼15 mV after CYP treatment. These data suggest that chronic inflammation induces somal hypertrophy and increases the excitability of C-fiber bladder afferent neurons by suppressing IA channels. Similar electrical changes in sensory pathways may contribute to cystitis-induced pain and hyperactivity of the bladder.