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Cardiac c-kit+ progenitor cells are important for maintaining cardiac homeostasis and can potentially contribute to myocardial repair. However, cellular physiology of human cardiac c-kit+ progenitor cells is not well understood. The present study investigates the functional store-operated Ca2+ entry (SOCE) channels and the potential role in regulating cell cycling and migration using confocal microscopy, RT-PCR, Western blot, coimmunoprecipitation, cell proliferation, and migration assays. We found that SOCE channels mediated Ca2+ influx, and TRPC1, STIM1, and Orai1 were involved in the formation of SOCE channels in human cardiac c-kit+ progenitor cells. Silencing TRPC1, STIM1, or Orai1 with the corresponding siRNA significantly reduced the Ca2+ signaling through SOCE channels, decreased cell proliferation and migration, and reduced expression of cyclin D1, cyclin E, and/or p-Akt. Our results demonstrate the novel information that Ca2+ signaling through SOCE channels regulates cell cycling and migration via activating cyclin D1, cyclin E, and/or p-Akt in human cardiac c-kit+ cells. [ABSTRACT FROM AUTHOR]

Adrenomedullin (ADM) is upregulated in cardiac tissue under various pathophysiological conditions, particularly in septic shock. The intra-cellular mechanisms involved in the effect of ADM on adult rat ventricular myocytes are still to be elucidated. Ventricular myocytes were isolated from adult rats 4 h after an intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg). Membrane potential and L-type calcium current (ICa,L) were determined using whole cell patch-clamp methods. APD in LPS group was significantly shorter than control values (time to 50% repolarization: LPS, 169 ± 2 ms; control, 257 ± 2 ms, P < 0.05; time to 90% repolarization: LPS, 220 ± 2 ms; control, 305 ± 2 ms, P < 0.05). ICa,L density was significantly reduced in myocytes from the LPS group (-3.2 ± 0.8 pA/pF) compared with that of control myocytes (-6.7 ± 0.3 pA/pF, P < 0.05). The ADM antagonist ADM-(22-52) reversed the shortened APD and abolished the reduction of ICa,L in shock myocytes. In myocytes from control rats, incubating with ADM for 1 h induced a marked decrease in peak ICa,L density. This effect was reversed by ADM-(22-52). The Gi protein inhibitor, pertussis toxin (PTX), the protein kinase A (PKA) inhibitor, KT-5720, and the specific cyclo-oxygenase 2 (COX-2) inhibitor, nimesulide, reversed the LPS-induced reduction in peak ICa,L. The results suggest a COX-2-involved PKA-dependent switch from G, coupled to PTX-sensitive Gi coupling by ADM in adult rat ventricular myocytes. The present study delineates the intracellular pathways involved in ADM-mediated effects on ICa,L in adult rat ventricular myocytes and also suggests a role of ADM in sepsis. [ABSTRACT FROM AUTHOR]

Investigates the transmural action potential (AP) and ionic current remodeling in ventricles of failing canine hearts. Remodeling of heterogeneous AP in ventricular cells of heart failure (HF); Early afterdepolarizations (EAD) in cells from failing hearts; Comparison with previous findings of ionic current remodeling in HF.