Elecrtophysiological properties of voltage-gated Ca^<2+> channel and other cation channels.

Ca^2+控制多种细胞过程，包括肌肉收缩、神经递质释放和其他形式的分泌、基因表达和细胞增殖。为了引起这些细胞反应，跨质膜的Ca^2+内流对增加胞质游离Ca^2+浓度（[Ca^2+] i）做出了主要贡献。除了特征明确的电压门控Ca^<2+>通道外，配体门控通道是主要的跨膜途径。ATP是P2 X受体的配体，是外周和中枢神经系统中神经递质或共递质的候选者。解剖学研究揭示了P2 X受体在大脑中的广泛分布。到目前为止，P2 X介导的突触反应已经在大脑的一些区域被记录。为了探讨突触后ATP受体在脑内的生理意义，我们用全细胞显微镜观察了急性分离的大鼠下丘脑弓状核神经元的P2 X反应。 ...更多信息 这是膜片钳技术的一部分。ATP浓度依赖性地诱发内向电流（Kd =42μM）。电流-电压关系显示在-10 mV左右开始出现明显的内向整流。P2受体激动剂300μM αβ-亚甲基-ATP和300μM βγ-亚甲基-ATP不能诱发内向电流，而100 μM ATPγS和100μM 2-甲硫基-ATP诱发内向电流，其幅度为100 μM ATP诱发内向电流的60%。P2受体拮抗剂PPADS呈浓度和时间依赖性地抑制ATP诱发的电流（2 min时Ki =19μM）。Ca^（2+）可抑制ATP诱发的电流，抑制范围为6.9mM，而Cd^（2+）（1-300 μM）则易化ATP诱发的电流，但解离速率较慢。在1-20 μM范围内，Zn^<2+>易化该电流，而在50 μM以上浓度时，Zn^<2+>抑制该电流。这些观察结果表明，功能性P2 X受体表达在下丘脑弓状核。少

Ca^<2+> controls diverse cellular processes, including muscle contraction, neurotransmitter release and other forms of secretion, gene expression, and cell proliferation. To evoke these cellular responses, Ca^<2+> influx across the plasma membrane makes a major contribution to augmenting the cytosolic free Ca^<2+> concentration ([Ca^<2+>]_i). In addition to the well-characterized voltage-gated Ca^<2+> channels, ligand-gated channels are the major transmembrane pathways. ATP, the ligand of P2X receptors, is a candidate of neurotransmitter or co-transmitter in the peripheral and central nervous system. Anatomical studies have revealed the wide distribution of P2X receptors in the brain. So far, P2X-mediated synaptic responses have been recorded in a few region of brain. To determine the physiological significance of postsynaptic ATP receptors in the brain, we have investigated the P2X responses in neurons acutely dissociated from rat hypothalamic arcuate nucleus by using the whole-cell m … More ode of the patch-clamp technique. ATP evoked inward currents in a concentration-dependent manner (K_d=42μM) at a holding potential of -70 mV. The current-voltage relationship showed a marked inward rectification starting around -10 mV. Although P2 receptor agonists, 300μM αβ-methylene-ATP and 300μM βγ-methylene-ATP did not induced any current, 100 μM ATPγS and 100μM 2-methylthio-ATP evoked inward currents of which amplitude was 60% of that evoked by 100 μM ATP. PPADS, P2 receptor antagonist, inhibited the ATP-evoked currents in a time- and concentration-dependent manner (K_i=19μM at 2 min). Permeant Ca^<2+> inhibited the ATP-evoked currents in the range of milimolars (K_i=6.9mM), however, Cd^<2+> (1-300 μM), a broad cation channel blocker, facilitated the currents with slow off-rate. Zn^<2+> in the range of 1-20 μM facilitated the current whereas Zn^<2+> at the concentrations over 50 μM inhibited the currents. These observations suggest that functional P2X receptors are expressed in hypothalamic arcuate nucleus. Less