Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes.
Sigma receptor ligands modulate contractility, Ca++ influx and beating rate in cultured cardiac myocytes.
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Sigma 受体配体调节培养心肌细胞的收缩力、Ca 流入和搏动率。
DOI：
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发表时间：
1994
影响因子：
3.5
通讯作者：
Y. Eilam
中科院分区：
文献类型：
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作者：
C. Ela;J. Barg;Z. Vogel;Y. Hasin;Y. Eilam
[~3H]-1，3-二邻甲苯基胍和(+)-[3H]-(3-hydroxyphenyl)-N-(1-propyl)-piperidine[(+)-3-PPP]与培养的新生大鼠心肌细胞膜的特异性结合表明心肌细胞上存在Sigma受体。将培养的心肌细胞暴露于纳摩尔浓度的(+)-3-PPP、(+)-五唑碱和氟哌啶醇中，可引起电起搏培养的心肌细胞收缩特性的特殊变化。细胞收缩运动幅度(ASM)在给药后1~2min下降10~25%，然后短暂升高(3~10min)，最后降至对照水平的75%左右。对负载Indo-1的心肌细胞的荧光测量显示，药物诱导的细胞内游离钙瞬变浓度([Ca++]i)的大小发生了变化，与ASM中观察到的变化相似。这些变化可能是通过~(45)Ca~(++)内流速率的相应变化来调节的。加入(+)-3-PPP后2~7min，~(45)Ca~(++)内流速率增加，之后降至对照水平的50%。用thapsigargin预先孵育，耗尽肌浆网-Ca++储存，并不影响随后添加(+)-3-PPP引起的ASM变化模式。这表明[Ca++]i的变化不是由肌浆网-Ca++转运系统介导的。暴露于Sigma配体不影响肌丝对Ca++的表观敏感性，这一点从ASM和[Ca++]i瞬变之间的关系中可以看出。没有节奏的文化会自发地以恒定的节奏收缩。Sigma受体配体引起搏动频率的变化，随后是不规则的收缩。
Specific binding of [3H]-1,3-di-o-tolylguanidine (DTG) and (+)-[3H]-(3-hydroxyphenyl)-N-(1-propyl)-piperidine [(+)-3-PPP] to membranes of cultured cardiac myocytes from neonatal rats revealed the presence of sigma receptors on these cells. Exposure of cultured cardiomyocytes to nanomolar concentrations of (+)-3-PPP, (+)-pentazocine and haloperidol induced specific patterns of changes in contractility of electrically paced cultures. The amplitude of systolic cell-motion (ASM) decreased by 10 to 25% 1 to 2 min after drug addition, then transiently increased (3-10 min) and finally decreased to about 75% of control level. Fluorescence measurements on indo-1 loaded cardiomyocytes revealed drug-induced changes in the size of the concentration of free cytosolic calcium ([Ca++]i)-transients, similar to the changes observed in ASM. These changes appear to be mediated by corresponding changes in the rates of 45Ca++ influx which increased 2 to 7 min after the addition of (+)-3-PPP and decrease to 50% of the control level thereafter. Preincubation with thapsigargin, which depletes the sarcoplasmic reticulum-Ca++ stores, did not affect the pattern of changes in ASM, induced by the subsequent addition of (+)-3-PPP. This indicates that the changes in [Ca++]i are not mediated by sarcoplasmic reticulum-Ca++ transport systems. Exposure to sigma ligands did not affect the apparent sensitivity of the myofilaments to Ca++, as indicated by the relationships between changes in ASM and in [Ca++]i-transients. Cultures which were not paced, contracted spontaneously at a constant rhythm. Sigma receptor ligands caused changes in beating frequencies which were followed by irregular contractions.(ABSTRACT TRUNCATED AT 250 WORDS)