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Aim: We compared the clinical and physiological consequences of the novel mutation R878C in a highly conserved pore residue in domain II (S5-S6) of human, hNa v 1.5, cardiac Na + channels.Methods: Full clinical evaluation of pedigree members through three generations of a Chinese family combined with SCN5A sequencing from genomic DNA was compared with patch and voltage-clamp results from two independent expression systems.Results: The four mutation carriers showed bradycardia, and slowed sinoatrial, atrioventricular and intraventricular conduction. Two also showed sick sinus syndrome; two had ST elevation in leads V1 and V2. Unlike WT-hNa v 1.5, whole-cell patch-clamped HEK293 cells expressing R878C-hNa v 1.5 showed no detectable Na + currents (i Na ), even with substitution of a similarly charged lysine residue. Voltage-clamped Xenopus oocytes injected with either 0.04 or 1.5 lg lL )1 R878C-hNa v 1.5 cRNA similarly showed no i Na , yet WT-hNa v 1.5 cRNA diluted to 0.0004-0.0008 ng lL )1 resulted in expression of detectable i Na . i Na was simply determined by the amount of injected WT-hNa v 1.5: doubling the dose of WT-hNa v 1.5 cRNA doubled i Na . i Na amplitudes and activation and inactivation characteristics were similar irrespective of whether WT-hNa v 1.5 cRNA was given alone or combined with equal doses of R878C-hNa v 1.5 cRNA therefore excluding dominant negative phenotypic effects. Na + channel function in HEK293 cells transfected with R878C-hNa v 1.5 was not restored by exposure to mexiletine (200 lm) and lidocaine (100 lm). Fluorescence confocal microscopy using E3-Nav1.5 antibody demonstrated persistent membrane expression of both WT and R878C-hNa v 1.5. Modelling studies confirmed that such i Na reductions reproduced the SSS phenotype. Conclusion: Clinical consequences of the novel R878C mutation correlate with results of physiological studies.

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The direct ink-jet printing of ceramic powders requires the development of highly fluid suspensions of ceramic particles with viscosity < 40 mPas. Here we describe the development of two such ceramic suspensions, which contain up to 30% by volume of PZT particles in either an azeotropic mixture of MEK and ethanol or in an alkane wax at 120 'C. The influence of various processing parameters on fluid theology are investigated and trial fluids have been passed through an ink-jet printing head.