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The effects of hypoxia and reoxygenation on action potentials (AP), contractions, and certain biochemical parameters were studied in isolated rat ventricular myocytes in monolayer culture in the presence and absence of glucose. Substrate deprivation alone had no influence on the basal properties. In the presence of glucose, a 4-h hypoxic treatment caused only a moderate decrease in AP amplitude and rate. In substrate-free conditions, hypoxia induced a gradual decline in plateau potential level and in AP duration and rate, followed by rhythm abnormalities and a failure of the electromechanical coupling. Spontaneous AP generation then ceased, and the resting potential decreased with increased duration of hypoxia. These alterations were associated with a decrease in ATP content, an increase in the lactate production, and a leakage of about 50% of the total cellular lactate dehydrogenase (LDH). Cells reoxygenated after 150 min hypoxia recovered near-normal function, while the ATP depletion ceased and the rate of lactate and LDH loss was diminished. Conversely, cells reoxygenated after 4 h hypoxia exhibited a further decrease of the residual resting polarization and no change in the decline of intracellular ATP and in the efflux of cytosolic lactate and LDH. The results of this study indicate that (1) the sequence and the extent of functional alterations are dependent on the duration of hypoxia in the absence of exogenous substrate and (2) ATP depletion and the amount of lactate and LDH released during hypoxia are related to the shift from reversibly to irreversibly damaged cells.

Background: Protein tyrosine phosphatase 1B (PTPN1) dephosphorylates insulin receptors and attenuates insulin signaling. Polymorphisms in the coding sequence of PTPN1 have been variably associated with type 2 diabetes (T2D). We hypothesized that variations within the PTPN1 promoter might contribute to the development of T2D and related metabolic traits. Methods: We screened 2.0 kb of PTPN1 promoter in 174 T2D patients and 412 controls using PCR and denaturing HPLC. Association analysis was performed between diabetes and related traits and single-nucleotide polymorphism genotypes. We functionally tested 2 variants (؊1023C>A and ؊51delA) by measuring their influence on luciferase activity in HepG2 cells and performing the electrophoretic mobility shift assay (EMSA). Results: One common (؊1023C>A) and 6 rare (؊51delA, ؊451A>G, ؊467T>C, ؊1045G>A, ؊1286-3bp-del, and ؊1291-9bp-del) variants were identified in

This study was carried out to investigate the influence of the membrane fatty acid composition on the basal electrical and contractile activities and the response to beta-adrenergic stimulation of rat cardiac muscle cells in culture. Cells were grown for 3 days in a conventional serum culture medium and then incubated for 24 h in synthetic media containing either n-6 or n-3 as the sole source of polyunsaturated fatty acids (PUFA). The n-6/n-3 ratio in the phospholipids was 0.9 in the n-3 cells and 13.1 in the n-6 cells compared with 6.3 in controls cells. Such modifications did not alter action potentials and the main parameters related to contraction, although shortening was slightly accelerated in the n-6 cells. On the other hand, the positive chronotropic effect induced by isoproterenol was more pronounced (P less than 0.01) in n-3 cells than in n-6 cells. In addition, isoproterenol caused a decrease in contraction duration and in shortening and relaxation time that was less pronounced in n-6 than in control cells (P less than 0.01, P less than 0.01 and P less than 0.05, respectively). These results suggest that the PUFA balance in the phospholipids may contribute to modulate the cardiac adrenergic receptor system but not the membrane properties related to electro-mechanical functions.

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