BIN1, Myotubularin, and Dynamin-2 Coordinate T-Tubule Growth in Cardiomyocytes.

Background: Transverse tubules (t-tubules) form gradually in the developing heart, critically enabling maturation of cardiomyocyte Ca homeostasis. The membrane bending and scaffolding protein BIN1 (bridging integrator 1) has been implicated in this process. However, it is unclear which of the various reported BIN1 isoforms are involved, and whether BIN1 function is regulated by its putative binding partners MTM1 (myotubularin), a phosphoinositide 3'-phosphatase, and DNM2 (dynamin-2), a GTPase believed to mediate membrane fission.

Sarcoplasmic Reticulum Calcium Release Is Required for Arrhythmogenesis in the Mouse.

Dysfunctional sarcoplasmic reticulum Ca handling is commonly observed in heart failure, and thought to contribute to arrhythmogenesis through several mechanisms. Some time ago we developed a cardiomyocyte-specific inducible SERCA2 knockout mouse, which is remarkable in the degree to which major adaptations to sarcolemmal Ca entry and efflux overcome the deficit in SR reuptake to permit relatively normal contractile function. Conventionally, those adaptations would also be expected to dramatically increase arrhythmia susceptibility.

Hypokalemia Promotes Arrhythmia by Distinct Mechanisms in Atrial and Ventricular Myocytes.

Rationale: Hypokalemia occurs in up to 20% of hospitalized patients and is associated with increased incidence of ventricular and atrial fibrillation. It is unclear whether these differing types of arrhythmia result from direct and perhaps distinct effects of hypokalemia on cardiomyocytes.

Objective: To investigate proarrhythmic mechanisms of hypokalemia in ventricular and atrial myocytes.

Gene Transfer in Isolated Adult Cardiomyocytes.

During the past few decades, gene delivery using recombinant virus has made tremendous progress. With a higher than 80 % transduction efficiency, even in non-dividing cells, viral transduction has become the method of choice for efficient gene transfer into cardiomyocytes. However, in vitro gene delivery is dependent on a robust cell isolation protocol, as prolonged cultivation is needed to initiate gene expression and target specific cellular processes.

A link between impaired purine nucleotide synthesis and apoptosis in Drosophila melanogaster.

The biosynthetic pathways and multiple functions of purine nucleotides are well known. However, the pathways that respond to alterations in purine nucleotide synthesis in vivo in an animal model organism have not been identified. We examined the effects of inhibiting purine de novo synthesis in vivo and in cultured cells of Drosophila melanogaster.