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P26 Purpose: Heart failure is associated with images of Di-8-ANEPPS stained myocytes. reduced sarco/endoplasmic reticulum cal- Specifically, Fourier analysis indicated cium ATPase (Serca) function. Recent stud- a maintained organization of t-tubules ies of mice with conditional cardiomyocyte- which transversely spanned the cell, but Oslo, Norway specific knockout of the Serca2 gene (KO) an increased presence of tubules in the Center for Heart Failure Research, revealed that major reductions in Serca2 longitudinal direction. Immunocytochemi- and SR function are compensated by en- cal data showed that the newly grown lon- hanced Ca2+ cycling over the cell mem- gitudinal t-tubules did not contain L-type brane. These compensations maintain Ca2+ channels. However they contained cardiac function at near-normal values, at Na+/Ca2+-exchangers least in the short term. We hypothesize that ryanodine receptors in the sarcoplasmic increased trans-sarcolemmal Ca2+ fluxes reticulum. These alterations were asso- are facilitated by alterations in sarcolemmal ciated with increased expression of the morphology. L-type Ca2+ channel (α ıC subunit = ı78% of Swift F, Enger UH, Jølle GF, Andersson KB, Christensen G, Sejersted OM, Louch WE Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, T-tubule proliferation facilitates transsarcolemmal Ca2+ flux to compensate for declining SR function in Serca2 KO mice University of Oslo, Norway with co-localized FF values) and Na+/Ca2+-exchanger (NCXı Methods: Ventricular cardiomyocytes were = 2ı6% FF). Peak L-type Ca2+ currents and isolated from KO hearts 7 weeks following NCX-mediated Ca2+ extrusion were also gene disruption. Serca2 flox-flox (FF) mice enhanced in KO. Electron micrographs served as controls. Myocyte structure and of fixed heart sections showed reduced electrophysiology were examined by stand- volume of the SR after KO. ard immunocytochemical and patch clamp techniques. Conclusions: Our observations indicate that proliferation of longitudinal t-tubules Results: Although cardiomyocyte dimen- facilitates trans-sarcolemmal Ca2+ flux to sions were unaltered in KO compared to compensate for declining SR function FF control values, total surface area was following Serca2 KO. increased (cell capacitance = ı82 pF vs ı47 pF, P<0.05). This resulted from increased t-tubule density, as revealed by confocal 8th Annual CHFR Symposium September 31 – October 01, 2010 Holmenkollen Park Hotel Rica Oslo, Norway Page 4 3