Glutathione accelerates sodium channel inactivation in excised rat axonal membrane patches

The effects of glutathione were studied on the gating behaviour of sodium channels in membrane patches of rat axons. Depolarizing pulses from –120 to –40 mV elicited sodium currents of up to 500 pA, indicating the simultaneous activation of up to 250 sodium channels. Inactivation of these channels in the excised, inside-out configuration was fitted by two time constants ( h1=0.81 ms; h2= 5.03 ms) and open time histograms at 0 mV revealed a biexponential distribution of channel openings ( short=0.28 ms; long=3.68 ms). Both, the slow time constant of inactivation and the long lasting single channel openings disappeared after addition of the reducing agent glutathione (2–5 mM) to the bathing solution. Sodium channels of excised patches with glutathione present on the cytoplasmatic face of the membrane had inactivation kinetics similar to channels recorded in the cell-attached configuration. These observations indicate that redox processes may contribute to the gating of axonal sodium channels

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction: The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods: A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results: 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions: The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Voltage-dependent blockade in Na+-dependent action potentials after β1- and H2-receptor stimulation in mammalian ventricular myocardium

In isolated papillary muscles of guinea pigs, the influence of isoproterenol, histamine, theophylline, and phenylephrine on the maximal rate of rise [Formula: see text] of Na+-dependent action potentials and on isometric contractile force was studied under rested state conditions. Isoproterenol (1 × 10−7 mol/L), histamine (2 × 10−5 mol/L), and theophylline (2 × 10−3 mol/L) shifted the voltage dependence of [Formula: see text] into the hyperpolarizing direction and, consequently, led to a voltage-dependent [Formula: see text] blockade. The α-adrenoceptor agonist phenylephrine, on the other hand, proved to be ineffective in depressing [Formula: see text]. The β-receptor blocker pindolol (4 × 10−6 mol/L) or the H2-receptor blocker cimetidine (4 × 10−5 mol/L) abolished the inhibitory effects of isoproterenol and histamine, respectively, and caused [Formula: see text] to return to the initial control value. A concentration–response relationship analysis at −65 mV revealed that isoproterenol exerted only a weak inhibitory effect on [Formula: see text] compared with its positive inotropic action. The IC50 value of the former effect amounted to approximately 5 × 10−6 mol/L, but the EC50 value of the latter effect was 4 × 10−8 mol/L. It is, therefore, concluded that, in physiologically relevant concentrations, β-adrenergic agonists are unlikely to significantly modulate Na+-dependent excitability even in partially depolarized myocardium. </jats:p