Abstract-A neuronal isoform of nitric oxide synthase (nNOS) has recently been located to the cardiac sarcoplasmic reticulum (SR). Subcellular localization of a constitutive NOS in the proximity of an activating source of Ca 2ϩ suggests that cardiac nNOS-derived NO may regulate contraction by exerting a highly specific and localized action on ion channels/transporters involved in Ca 2ϩ cycling. To test this hypothesis, we have investigated myocardial Ca 2ϩ handling and contractility in nNOS knockout mice (nNOS Ϫ/Ϫ ) and in control mice (C) after acute nNOS inhibition with 100 mol/L L-VNIO. nNOS gene disruption or L-VNIO increased basal contraction both in left ventricular (LV)
The G-protein coupled receptors (GPCRs) superfamily comprise similar proteins arranged into families or classes thus making it one of the largest in the mammalian genome.
Significance (p) 0.005 <0.001 0.005 Regression coefficient -0.023 0.018 -0.032 1998). The purpose of the present experiments was therefore to investigate the effects of tetracaine on [Ca"], in cells which were overloaded with calcium to the point where they displayed spontaneous release between stimuli. This was achieved in three different ways: (i) elevating external Ca concentration from 1 to 5 mM; (ii) the addition of 1 mM ouabain; (iii) addition of isoprenaline (1 pM). In all cases tetracaine (50-100 pM) abolished spontaneous Ca release without decreasing the amplitude of the systolic Ca transient. These results show that depression of RyR open probability can be used to selectively remove the untoward arrhythmogenic effects of inotropic agents.
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