Maintenance of Ca_i²⁺transients during prolonged cardiac arrest aids rapid contractile recovery

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• 作者：Horackova ; Magda ; Byczko ; Zenobia ; Morash ; Barbara
• 关键词：(Guinea pig) ; 2 ; 3-Butanedione monoxime ; Ca_i²⁺ transient ; Fura 2-acetoxymethyl (AM) ester ; Long-term culture ; Contractility ; Ultrastructure
• 刊名：European Journal of Pharmacology
• 出版年：2000
• 出版时间：September 22, 2000
• 年：2000
• 卷：404
• 期：3
• 页码：247-257
• 全文大小：2.55 M

文摘

We explored the effects of contractile arrest maintained for 24–72 h in the presence of 2,3-butanedione monoxime or a Ca²⁺ channel blocker (nifedipine or verapamil) on contractile activity, Ca_i²⁺ transients, and myofibrillar protein content and ultrastructure in long-term cultures of spontaneously beating adult guinea-pig cardiomyocytes. The contractions were not affected by 5 mM 2,3-butanedione monoxime, but they were strongly or fully suppressed by 10 and 18 mM 2,3-butanedione monoxime, respectively, while the Ca_i²⁺transients triggered by the maintained spontaneous electrical activity were either not changed at all (5 and 10 mM 2,3-butanedione monoxime) or decreased only slightly (18 mM 2,3-butanedione monoxime). The uncoupling of excitation from contraction by 10–18 mM for 24–72 h did not affect the content of the myofibrillar proteins. Confocal laser microscopy showed that these exposures affected the assembly of myofilaments, giving an overall deranged appearance to the myofibrils. In spite of this effect, the cells' contractile activity was readily regained within 15–60 min upon the washout of 2,3-butanedione monoxime. The 24–72-h exposures to 5 μM nifedipine or 10 μM verapamil, which blocked fully both the Ca_i²⁺ transients and contractility, did not affect the myofibrillar protein content nor their assembly. However, the recovery of contractile activity after exposure to a Ca²⁺-channel blocker was significantly slower (several days) than after 2,3-butanedione monoxime exposure. Furthermore, cultures exposed to Ca²⁺-channel blockers also had significantly decreased sensitivity to β-adrenergic stimulation. Altogether, these data indicate the importance of regular Ca²⁺ influx for the maintenance of the functional integrity of adult cardiomyocytes during prolonged periods of contractile arrest.