Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons
Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in rat sensory neurons
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DOI：
10.1007/s00424-011-1023-5
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发表时间：
2011-11-01
影响因子：
4.5
通讯作者：
Ursu, Daniel
中科院分区：
文献类型：
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作者：
Comunanza, Valentina;Carbone, Emilio;Ursu, Daniel
我们研究了辣椒素激活瞬时受体电位 vanilloid-1 (TRPV1) 对大鼠 DRG 感觉神经元低电压激活 (LVA, T 型) Ca2+ 通道和高电压激活 (HVA; L, N, P/Q, R) 电流的抑制作用，作为辣椒素诱导镇痛的潜在机制。使用在暴露于 1 μM 辣椒素 30 秒之前和之后施加的斜坡命令，在全细胞钳位的 DRG 神经元中引发 T 型和 HVA 电流。 T 型电流在 I-V 特性的第一个峰值处估计，HVA 在第二个峰值处估计，发生在更正的电位处。中小型 DRG 神经元对辣椒素作出反应，产生不同幅度的瞬时内向电流，主要由 Ca2+ 携带。在那些以大量 Ca2+ 流入（占总数的 59%）响应辣椒素的细胞中，观察到 T 型和 HVA Ca2+ 电流的显着抑制。在应用辣椒素期间用 Ba2+ 替代 Ca2+ 或应用高剂量的细胞内 BAPTA (20 mM) 可以阻止 T 型和 HVA 通道抑制的百分比，这表明 TRPV1 介导的 T 型和 HVA 通道抑制是 Ca2+ 依赖性的，并且可能仅限于膜纳米微区。我们的数据与 TRPV1 诱导的镇痛可能源自 T 型和 HVA 通道的间接抑制的观点一致，这反过来又会降低伤害性信号生成（T 型通道抑制）和伤害性突触传递（HVA 通道抑制）的阈值。
We studied the inhibitory effects of transient receptor potential vanilloid-1 (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca2+ channel and high-voltage-activated (HVA; L, N, P/Q, R) currents in rat DRG sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia. T-type and HVA currents were elicited in whole-cell clamped DRG neurons using ramp commands applied before and after 30-s exposures to 1 mu M capsaicin. T-type currents were estimated at the first peak of the I-V characteristics and HVA at the second peak, occurring at more positive potentials. Small and medium-sized DRG neurons responded to capsaicin producing transient inward currents of variable amplitudes, mainly carried by Ca2+. In those cells responding to capsaicin with a large Ca2+ influx (59% of the total), a marked inhibition of both T-type and HVA Ca2+ currents was observed. The percentage of T-type and HVA channel inhibition was prevented by replacing Ca2+ with Ba2+ during capsaicin application or applying high doses of intracellular BAPTA (20 mM), suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca2+-dependent and likely confined to membrane nano-microdomains. Our data are consistent with the idea that TRPV1-induced analgesia may derive from indirect inhibition of both T-type and HVA channels which, in turn, would reduce the threshold of nociceptive signals generation (T-type channel inhibition) and nociceptive synaptic transmission (HVA-channels inhibition).