糖尿病大鼠心脏乳头肌收缩对细胞内pH变化的敏感性降低。

Decreased sensitivity of contraction to changes of intracellular pH in papillary muscle from diabetic rat hearts.

作者信息

Lagadic-Gossmann D, Feuvray D

机构信息

Laboratoire de Physiologie Comparée, Centre National de la Recherche Scientifique, Université Paris XI, Orsay, France.

出版信息

J Physiol. 1990 Mar;422:481-97. doi: 10.1113/jphysiol.1990.sp017996.

DOI:10.1113/jphysiol.1990.sp017996

PMID:2352189

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1190144/

Abstract

The relationship between intracellular pH (pHi) and contractile activity was investigated in papillary muscles isolated from right ventricle of normal and streptozotocin (STZ)-induced diabetic rats. pHi changes induced by 20 mM-NH4Cl were recorded with H(+)-sensitive microelectrodes. 2. An increase in pHi of approximately 0.20 pH units on exposure to NH4Cl led to an increase of the maximum developed tension, which was 707.8 +/- 57.5% (mean +/- S.E. of mean, n = 10) of control in normal muscles and 271 +/- 16.3% (n = 10) in diabetic muscles. On the other hand, acidosis induced by NH4Cl withdrawal was associated with a fall in developed tension to 48.2 +/- 6.7% of control in diabetic muscles, as compared to 79.2 +/- 8% in normal muscles. 3. The decrease in tension associated with acidosis was rapidly followed (in approximately 2 min) by a transient redevelopment of force, which peaked at 80.2 +/- 8.6% of control in the diabetic muscles as compared to 153.5 +/- 11.7% in normal papillary muscles. The peak of this secondary positive inotropy coincided in both groups of muscles with the maximum decrease of pHi, i.e. -0.40 +/- 0.02 and -0.28 +/- 0.04 pH units in diabetic and normal muscles, respectively. 4. Caffeine (10 mM), which had a marked positive inotropic effect in both groups of muscles, abolished the transient recovery of tension occurring after NH4Cl withdrawal. Ryanodine (2 microM) which had a marked negative inotropic effect on both normal and diabetic papillary muscles, also suppressed the transient recovery of tension. 5. The presence of amiloride (1 mM) during acidosis induced by NH4Cl withdrawal abolished the observed differences in developed tension, in particular the transient recovery of tension, between normal and diabetic muscles, as it abolished the differences in the amplitude of pHi decrease and in the time course of pHi recovery. 6. The presence of 2',4'-dichlorobenzamil amiloride (40 microM) significantly and similarly delayed and reduced the amplitude of transient recovery of tension in both normal and diabetic papillary muscles. 7. We conclude that STZ-induced diabetes induces a decrease in pHi sensitivity of contractile force. This may be the consequence of a change in sarcoplasmic reticulum (SR) composition and function, and may also indirectly result from changes in Na(+)-H+ exchange activity, particularly during intracellular acidosis.

摘要

研究了从正常大鼠和链脲佐菌素（STZ）诱导的糖尿病大鼠右心室分离的乳头肌中细胞内pH值（pHi）与收缩活性之间的关系。用H⁺敏感微电极记录20 mM - NH₄Cl诱导的pHi变化。2. 暴露于NH₄Cl时，pHi升高约0.20个pH单位导致最大收缩张力增加，正常肌肉中为对照的707.8±57.5%（平均值±平均标准误，n = 10），糖尿病肌肉中为271±16.3%（n = 10）。另一方面，NH₄Cl撤除诱导的酸中毒与糖尿病肌肉中收缩张力降至对照的48.2±6.7%相关，而正常肌肉中为79.2±8%。3. 与酸中毒相关的张力降低后迅速（约2分钟内）出现短暂的力再发展，糖尿病肌肉中峰值为对照的80.2±8.6%，而正常乳头肌中为153.5±11.7%。两组肌肉中这种继发性正性肌力作用的峰值与pHi的最大降低同时出现，即糖尿病肌肉和正常肌肉中分别为-0.40±0.02和-0.28±0.04 pH单位。4. 咖啡因（10 mM）在两组肌肉中均有明显的正性肌力作用，消除了NH₄Cl撤除后出现的张力短暂恢复。ryanodine（2 μM）对正常和糖尿病乳头肌均有明显的负性肌力作用，也抑制了张力的短暂恢复。5. 在NH₄Cl撤除诱导的酸中毒期间存在氨氯地平（1 mM）消除了正常和糖尿病肌肉之间在收缩张力方面观察到的差异，特别是张力的短暂恢复，因为它消除了pHi降低幅度和pHi恢复时间进程方面的差异。6. 2',4'-二氯苯甲酰胺氨氯地平（40 μM）的存在显著且类似地延迟并降低了正常和糖尿病乳头肌中张力短暂恢复的幅度。7. 我们得出结论，STZ诱导的糖尿病导致收缩力对pHi的敏感性降低。这可能是肌浆网（SR）组成和功能变化的结果，也可能间接源于Na⁺-H⁺交换活性的变化，特别是在细胞内酸中毒期间。