title: N-n-butyl haloperidol iodide preserves cardiomyocyte calcium homeostasis during hypoxia/ischemia.
abstract: OBJECTIVE
  N-n-Butyl haloperidol iodide (F(2)) is a novel compound derived from haloperidol. In our previous work, F(2) was found to be an L-type calcium channel blocker which played a protective role in rat heart ischemic-reperfusion injury in a dose-dependent manner. In the current study, we aimed to investigate the effects and some possible mechanisms of F(2) on calcium transients in hypoxic/ischemic rat cardiac myocytes.
  
  
  RESULTS
  Calcium transients' images of rat cardiac myocytes were recorded during simulated hypoxia, using a confocal calcium imaging system. The amplitude, rising time from 25% to 75% (RT25-75), decay time from 75% to 25% (DT75-25) of calcium transients, and resting [Ca(2+)](i) were extracted from the images by self-coding programs. In this study, hypoxia produced a substantial increase in diastolic [Ca(2+)](i) and reduced the amplitude of calcium transients. Both RT25-75 and DT75-25 of Ca(2+) transients were significantly prolonged. And F(2) could reduce the increase in resting [Ca(2+)](i)and the prolongation of RT25-75 and DT75-25 of Ca(2+) transients during hypoxia. F(2) also inhibited the reduction in amplitude of calcium transients which was caused by 30-min hypoxia. The activity of SERCA2a (sarcoplasmic reticulum Ca(2+)-ATPase, determined by test kits) decreased after 30-min ischemia, and intravenous F(2) in rats could ameliorate the decreased activity of SERCA2a. The inward and outward currents of NCX (recorded by whole-cell patch-clamp analysis) were reduced during 10-min hypoxia, and F(2) further inhibited the outward currents of NCX during 10-min hypoxia. All these data of SERCA2a and NCX might be responsible for the changes in calcium transients during hypoxia.
  
  
  CONCLUSIONS
  Our data suggest that F(2) reduced changes in calcium transients that caused by hypoxia/ischemia, which was regarded to be a protective role in calcium homeostasis of ventricular myocytes, probably via changing the function of SERCA2a.
authors.affiliation: Department of Pharmacology, Shantou University Medical College, 22 Xinling Road, Shantou, PR China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xiao
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wang
authors.forename: Yong-Pan
authors.initials: YP
authors.lastname: Huang
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Shen
authors.forename: Fen-Fei
authors.initials: FF
authors.lastname: Gao
authors.forename: Zhan-Qin
authors.initials: ZQ
authors.lastname: Huang
authors.forename: Yan-Shan
authors.initials: YS
authors.lastname: Zheng
authors.forename: Gang-Gang
authors.initials: GG
authors.lastname: Shi
mesh_terms: D000814:Aniline Compounds / Q000032:analysis; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000032:analysis; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006706:Homeostasis; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D007511:Ischemia / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D018613:Microscopy, Confocal; D057054:Molecular Imaging; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism*; D014966:Xanthenes / Q000032:analysis
chemical_list: D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C409648:Fluo 4; D005456:Fluorescent Dyes; C482574:N-n-butyl haloperidol iodide; D014966:Xanthenes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D006220:Haloperidol; D002118:Calcium