Factors influencing differentiation and development of ionic channels in cardiac muscle

影响心肌离子通道分化和发育的因素

• 批准号: 02454138
• 负责人: NISHI Katsuhide
• 金额: $ 1.54万
• 依托单位: KUMAMOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02454138/
• 关键词: cardiac action potential; ionic channel in excitable membrane; inplannted myocardium; gut pacemaker mechanism; protooncogene c-kit; protein tyrosinekinase; intestinal smooth muscle; developmental process of intestinal movement; 腸管平滑節細胞; 腸管ペースメーカー

Developmental changes in contractile responses of the isolated ileum of BALB/c mice treated with an antagonistic anti c-kit monoclonal antibody (ACK2) to bradykinin (BK) and acetylcholine (ACh) were examined in vitro. Isolated ileum longitudinal muscle of new-born mice (BALB/c) started to show regular rhythmic contraction 4 days after birth, but pre-treatment with ACK2 for 4 days postnatally resulted in failure of postnatal development of the regular activity of the intestine. ACH(10^<-8>M>) induced sustained contraction in a dose-dependent manner in both ACK2 treated and control ileum obtained from mice of the same age group. The sensitivity to ACh was augmented in the ACK2-treated group. The response to ACh was blocked by atropine (10^<-7>M). BK(8x10^<-11>M) produced marked contraction followed by relaxation in the ACK2-treated ileum, while in the control ileum the agent (8x10^<-9>M) induced only a small transient increase in the amplitude of spontaneous contraction. Tetrodotoxin (10^<-7>M) did not alter the response to BK in both ACK2 treated and control groups. Voltage-clamp analyses of the Ca^<2+>-dependent ionic currents in dissociated smooth muscle cells from mice treated with or without ACK2 also revealed developmental differences in both ACh and BK responses. These findings suggest that c-kit expressing cells play a crucial role in development of intracellular mechanisms for Ca^<2+> handing for contraction and relaxation in intestinal smooth muscle or in membrane sensitivity to BK and other substances.

用抗c-kit单克隆抗体（ACK 2）处理BALB/c小鼠离体回肠，观察其对缓激肽（BK）和乙酰胆碱（ACh）收缩反应的发育性变化。新生小鼠（BALB/c）的离体回肠纵肌在出生后4天开始显示有规律的节律性收缩，但出生后用ACK 2预处理4天导致出生后肠的有规律活动的发育失败。ACH（10 μ <-8>M）以剂量依赖性方式在从相同年龄组的小鼠获得的ACK 2处理的回肠和对照回肠中诱导持续收缩。ACh的敏感性在ACK 2治疗组中增加。阿托品（10 μ M）可阻断ACh的反应<-7>。BK（8 × 104 μ <-11>M）在ACK 2处理的回肠中产生显著的收缩，随后是舒张，而在对照回肠中，该试剂（8 × 104 μ <-9>M）仅诱导自发收缩幅度的短暂增加。河豚毒素（10 μ <-7>M）在ACK 2处理组和对照组中均不改变对BK的应答。电压钳分析显示，在ACh和BK反应的发育过程中，ACh和BK反应都存在差异。这些发现表明，表达c-kit的细胞在肠平滑肌收缩和舒张的Ca^2+处理的细胞内机制的发展中或在膜对BK和其他物质的敏感性中起关键作用。

项目成果

K.Nishi,J.Muramoto,H.Araki: "Developmental changes in action potential of rat myocardium transplanted into the renal capsular space" Japanese Journal of Physiology.

K.Nishi，J.Muramoto，H.Araki：“移植到肾囊间隙的大鼠心肌动作电位的发育变化”日本生理学杂志。

Nobuo Hotokebuchi: "Acceleration of H^+ Extrusion via Na^+-H^+ Exchange in Guinea-Pig Ventricular Papillary Muscle under Intracellular Acidic Condition" Japanese Journal of Physiology. 41. 369-384 (1991)

Nobuo Hotokebuchi：“细胞内酸性条件下豚鼠心室乳头肌中 Na^ -H^ 交换加速 H^ 挤出”《日本生理学杂志》。

H.Maeda,A.Yamagata,S.Nishikawa,S.Kobayashi,K.Nishi: "Reguirement of Cーkit for development of intestinal pacemaker system" Nature.

H. Maeda、A. Yamagata、S. Nishikawa、S. Kobayashi、K. Nishi：“Ckit 对肠道起搏器系统开发的要求”自然。

JUN-ICHI MURAMOTO: "Developmental Changes in Electrophysiological Properties of Fetal Rat Myocardium Transplan ted into Renal Capsulal Space of Adult Rat" KUMAMOTO MEDICAL JOURNAL. 44(3). (1993)

JUN-ICHI MURAMOTO：“胎鼠心肌移植到成年大鼠肾囊腔中的电生理特性的发育变化”熊本医学杂志。

K.Nishi;J.Muramoto;H.Araki: "Depvelopmental changes in action potential of rat myocardium transplanted into the renal capsular space" Japanese Journal of Physiology.

K.Nishi;J.Muramoto;H.Araki：“移植到肾囊间隙的大鼠心肌动作电位的发展变化”日本生理学杂志。