Biomedical subjects

Song Wu

Publications and source records attributed to Song Wu.

21 records · Page 2Linked to original sources

PubMed2002

Aprikalim reduces the Na+-Ca2+ exchange outward current enhanced by hyperkalemia in rat ventricular myocytes.

BACKGROUND: [corrected] Aprikalim, an adenosine triphosphate (ATP) sensitive K+ (K(ATP)) channel opener, attenuates the elevation of intracellular Ca2+ concentration ([Ca2+]i) and improves the contractile functions after hyperkalemic and hypothermic cardioplegia. There is evidence that cardioplegia increases the Na+-Ca2+ exchange activity without affecting Ca2+ influx through L-type Ca2+ channels or Ca2+ content in the sarcoplasmic reticulum, the intracellular Ca2+ store. METHODS: We measured the Na+-Ca2+ exchange outward current with the patch-clamp technique in single rat ventricular myocytes exposed to hyperkalemia and hypothermia in the presence of aprikalim. The intracellular calcium concentration ([Ca2+]i) during cardioplegia, and the contractile function and [Ca2+]i transients induced by electrical stimulation or caffeine during rewarming and reperfusion in single ventricular myocytes were also determined. Contraction and [Ca2+]i were determined with video tracking and spectrofluorometry, respectively. RESULTS: Aprikalim, 100 micromol/L, the effect of which was blocked by glibamclamide, a K(ATP) inhibitor, significantly attenuated the hyperkalemia-elevated Na+-Ca2+ exchange current by 26% and 11% at 22 degrees C and 4 degrees C, respectively. Aprikalim also attenuated significantly the [Ca2+]i elevated during cardioplegia. Furthermore aprikalim significantly attenuated the reduction in amplitude and prolongation in duration of contraction of myocytes after cardioplegia. The effects of aprikalim mimicked those of nickle (Ni2+), a Na+-Ca2+ exchange blocker. The electrically or caffeine-induced [Ca2+]i transients were unaltered by cardioplegia or aprikalim. CONCLUSIONS: Aprikalim attenuates the Na+-Ca2+ exchange outward current elevated by hyperkalemia, which may attenuate the [Ca2+]i elevation during hyperkalemia and improve the contractile function after cardioplegia in the ventricular myocyte. The study provides further support that addition of a K(ATP) channel opener to the cardioplegic solution may produce beneficial effects in open heart surgery.

Adenosine Triphosphate↗

PubMed2002

Role of protein kinase C-epsilon in the development of kappa-opioid receptor tolerance to U50,488H in rat ventricular myocytes.

The role of protein kinase C-epsilon (PKC-epsilon) in the development of kappa-opioid receptor (kappa-OR) tolerance to the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]cyclohexyl) (U50,488H), the selective agonist of kappa-OR, was determined in rat ventricular myocytes. Incubation of ventricular myocytes with 1 microM U50,488H for 24 h significantly attenuated the inhibitory effects of 30 microM U50,488H on the electrically-induced [Ca(2+)](i) transient and forskolin-stimulated cyclic AMP accumulation, indicating the development of tolerance to the kappa-OR agonist. Chronic treatment of ventricular myocytes with U50,488H also induced translocation of PKC-epsilon to the particulate fraction. On the other hand, administration of 30 microM U50,488H for 10 min induced translocation of PKC-alpha to the particulate fraction in naïve ventricular myocytes, but not in cells pretreated with 1 microM U50,488H for 24 h. In ventricular myocytes incubated for 24 h with 1 microM U50,488H together with 1 microM chelerythrine or 1 microM GF109203X, PKC inhibitors, or 0.1 microM epsilonV1-2 peptide, a selective inhibitor of PKC-epsilon, 30 microM U50,488H still produced the inhibitory effect on the electrically-induced [Ca(2+)](i) transient as it did in naïve ventricular myocytes. Chronic treatment of ventricular myocytes with U50,488H and chelerythrine also attenuated the development of tolerance to acute U50,488H on cyclic AMP accumulation. Cells exposed to chelerythrine, GF109203X, or epsilonV1-2 peptide alone did not show an altered [Ca(2+)](i) response to U50,488H. These results indicate that activation of PKC-epsilon is a critical step in the development of tolerance in the kappa-OR.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMedDate not supplied

Role of kappa opioid receptor in cardioprotection of preconditioning: implications in cardiac surgery.

Kappa-opioid receptor mediates both immediate and delayed cardioprotection of ischemic/metabolic inhibition preconditioning. Both PKC and mitochondria ATP-sensitive K+ channel, mediate the protective action of kappa-opioid receptor stimulation. In delayed cardioprotection, PKC-epsilon may produce its effect via mitochondria ATP-sensitive K+ channel, and a stress inducible heat stress protein 70 may also be involved. Metabolic inhibition causes cell death which is accompanied by Ca2+ overload and mobilization of Ca2+ from sarcoplasmic reticulum to cytoplasm. The altered Ca2+ homeostasis is restored partially by kappa-opioid receptor or metabolic inhibition preconditioning. The finding indicates that opioids such as morphine may be used in the treatment of ischemic heart diseases and in open heart surgery.

Analgesics, Opioid↗