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Numerous ligands of sigma receptors are known to prolong the QT interval and therefore cause a variety of arrhythmias. High affinity binding sites for the prototypical sigma ligand haloperidol were found in membranes of cardiac myocytes from adult rats. Activation of sigma 1 receptor leads to a release of calcium from the endoplasmic reticulum that follows increased synthesis of inositol 1,4,5-trisphosphate (IP3). We studied the effect of long-term haloperidol treatment on the expression of sigma 1 receptors, IP3 receptors of type 1 and 2 in the individual parts of the rat heart, in isolated rat cardiomyocytes and in PC12 cells. We have found that prolonged treatment with haloperidol significantly increased mRNA levels of sigma 1 receptors in both atria and ventricles. Sigma 1 receptor's mRNA was increased also in isolated cardiomyocytes. Haloperidol treatment affects the expression of IP3 receptors of type 1 and 2 in cardiac atria, but not in cardiac ventricles. We observed increase in IP3 receptors in differentiated PC12 cells, but not in isolated cardiomyocytes. We propose that this increase might participate in triggering cardiac arrhythmias during haloperidol treatment, which has to be further verified.

MeSH
antipsychotika farmakologie MeSH
buňky PC12 MeSH
haloperidol farmakologie MeSH
inositol-1,4,5-trisfosfát - receptory genetika metabolismus MeSH
kardiomyocyty účinky léků metabolismus MeSH
krysa rodu rattus MeSH
messenger RNA genetika metabolismus MeSH
potkani Wistar MeSH
regulace genové exprese účinky léků MeSH
srdeční komory účinky léků metabolismus MeSH
srdeční síně účinky léků metabolismus MeSH
zvířata MeSH
Check Tag
krysa rodu rattus MeSH
mužské pohlaví MeSH
zvířata MeSH
Publikační typ
časopisecké články MeSH
práce podpořená grantem MeSH

Článek

Effects of voltage sensitive dye di-4-ANEPPS on guinea pig and rabbit myocardium

General physiology and biophysics. 2008 ; 27 (1) : 45-54.

Gen Physiol Biophys
ISSN 0231-5882
Medvik
Zdroj

Voltage-sensitive dyes (VSDs) are used to record transient potential changes in various cardiac preparations. In our laboratory, action potentials have been recorded by optical probe using di-4-ANEPPS. In this study, the effects of two different ways of staining were compared in guinea pig and rabbit isolated hearts perfused according to Langendorff: staining either by coronary perfusion with low dye concentration or with concentrated dye as a bolus into the aorta. Staining with low dye concentration lead to its better persistence in the tissue. Electrogram and coronary flow were monitored continuously. During the staining and washout of the dye, prominent electrophysiological changes occurred such as a decrease in spontaneous heart rate, partial atrioventricular block and changes of ST-T segment, accompanied by a decrease in mean coronary flow. No production of hydroxyl radicals was found by HPLC which excluded significant ischemic damage of the myocardium. Good viability of the stained preparation was supported by unchanged electron microscopy. Since in rabbit hearts the VSD-induced arrhythmogenesis was less pronounced, we conclude that the rabbit myocardium is more resistant to the changes triggered by VSD application. It may be due to different properties of the membrane potassium channels in the cardiomyocytes of these two species.

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