Analysis of ionic channels involved in burst generation of respiratory neurons in newborn rat medulla in vitro.

体外新生大鼠髓质呼吸神经元爆发性生成中涉及的离子通道分析。

• 批准号: 07680883
• 负责人: ONIMARU Hiroshi
• 金额: $ 0.26万
• 依托单位: Showa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07680883/
• 关键词: Respiratory neurons; Respiratory rhythm; Calcium channel; Potassium channel; Sodium channel; Medulla oblongata; Newborn rat; in vitro; イオンチャネル; ラット

Respiratory neurons in the ventrolateral medulla have high threshold (N,L types), intermediate threshold (P type) and low threshold (T type) Ca^<2+> channels. Using patch clamp method, we investigated high and intermediate throshold Ca^<2+> channels and Ca^<2+>-dependent K^+ channels which are thought to be important in the burst generation, and persistent Na^<2+> channels which are related to intrinsic oscillation of membrane potentials.[Result] 1) Application of P-type Ca channel blocker, omega-Aga-IVA (0.2muM), reduced the burst amplitude. 2) N-type Ca^<2+> channel blocker, omega-CgTx (2muM) increased the burst amplitude and caused partial inactivation of action potentials. omega-CgTx also reduced spike after-hyperpolarization, probably owing to indirect blockade of Ca^<2+>-dependent K^+ channels. 3) Ca^<2+>-dependent K^+ channel blocker, apamine (0.4-1muM) induced an increase in the burst amplitude and partial inactivation of action potentials. 4) L-type Ca^<2+> channel blocker, ni … More fedipine (20muM) shortened the burst duration. 5) After complete inhibition of the burst activity due to Ca^<2+> channel blockade by 0.1 mM Cb^<2+>, Pre-I neurons showed slow depolarizing responses and depolarization-dependent membrane oscillation. The activation threshold was around-45 mV.Subsequent K^+ channel blockade produced spontaneous bursting activity and depolarizing plateau potentials. These responses were blocked by 0.5muM TTX superfusion. [Discussion] We suggest ionic mechanisms of the burst generation as follows : Intrinsic slow depolarization in Pre-I neurons due to activation of TTX-sensitive persistent Na^<2+> channels and P-type Ca^<2+> channels is important in rising phase of burst activity. Then, N and L-Type Ca^<2+> channels are activated to augment the burst. Ca^<2+>-dependent K^+ channels are thought to participate in maintenance and termination of the burst activity. [Conclusion] We revealed ion channels in respiratory neurons in the ventrolateral medulla and suggested function of these channels for the burst generation. Less

延髓腹外侧区呼吸神经元有高阈值(N，L型)、中阈值(P型)和低阈值(T型)钙通道。[结果]1)应用P型钙通道阻断剂omega-Aga-IVA(0.2muM)可降低猝发的幅度。(2)N-型钙通道阻断剂omega-CgTx(2muM)可使动作电位部分失活。Omega-CgTx也能抑制后超极化，这可能是由于间接阻断依赖于钙离子的钾通道所致。(3)钙依赖性钾通道阻断剂阿帕明(0.4-1µM)可使动作电位的爆发幅度增加，部分失活。4)L型钙通道阻滞剂，Ni…较多的非地平(20µM)可缩短阵发性发作持续时间。(5)0.1mM Cb~(2+)和Gt~(2+)通道阻断后，Pre-I神经元表现出缓慢的去极化反应和去极化依赖性的膜振荡。激活阈值在-45 mV左右，随后阻断K~+通道产生自发爆发活动和去极化平台电位。0.5muMTTX灌流可阻断上述反应。[讨论]我们认为爆发产生的离子机制如下：在爆发活动的上升期，TTX敏感的持续性Na~(2+)通道和P型Ca~(2+)&gt~(2+)通道激活的前I区神经元的内源性慢去极化是重要的。然后，N和L型钙离子通道被激活以增强猝发。钙依赖的K^+通道被认为参与了突发活动的维持和终止。[结论]我们在延髓腹外侧区的呼吸神经元中发现了离子通道，并推测了这些通道在猝发发生中的作用。较少

项目成果

Onimaru,H.: "Optical imaging of respiratory burst activity in newborn rat medullary block preparations." Neurosci,Res.25. 183-190 (1996)

Onimaru,H.：“新生大鼠髓质块制剂中呼吸爆发活动的光学成像。”

Onimura, H.: "Studies of the respiratory center using isolated brainstem-spinal cord preparations." Neurosci.Res. 21. 183-190 (1995)

Onimura, H.：“使用分离的脑干脊髓制剂对呼吸中枢进行研究。”

Hiroshi Onimaru: "Intrinsic burst generation of peinspiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats" Exp. Brain Res.106. 57-68 (1995)

Hiroshi Onimaru：“从新生大鼠中分离出的脑干脊髓制剂的髓质中呼吸神经元的内在爆发”实验。

Onimaru,H.: "Studies of the respiratory center using isolated braiusten-spinal cord preparations" Neurosci.Res.21. 183-190 (1995)

Onimaru,H.：“使用分离的布劳斯滕脊髓制剂对呼吸中枢的研究”Neurosci.Res.21。

Onimaru,H.: "Intrinsic burst generation of preinspiratory neurons in the medulla of brainstew-spinal cord preparations isolated from newborn rats." Exp.Brain Res.106. 57-68 (1995)

Onimaru,H.：“从新生大鼠中分离出的脑炖脊髓制剂的髓质中吸气前神经元的内在爆发性生成。”