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Langberg, J.

Publications and source records attributed to Langberg, J..

2 recordsLinked to original sources

Generation of Monophasic Action Potentials and Intermediate Forms

The Monophasic Action Potential (MAP) is a near replica of the transmembrane potential recorded when an electrode is pushed firmly against cardiac tissue. Despite its many practical uses, the mechanism of MAP signal generation and the reason it is so different from unipolar recordings is not completely known and is a matter of controversy. It is hypothesized that partial depolarization of the cells directly underneath the electrode contributes to the generation of MAP signals. In this paper, we describe a parametric, semi-quantitative method to generate realistic MAP and intermediate forms - multiphasic electrograms different from an ideal MAP - that does not require the partial depolarization hypothesis. The key ideas of our method are the formation of junctional spaces, i.e., electrically isolated pockets between the surface of an electrode and tissue, and the presence of a complex network of passive components that acts as a high-pass filter to distort the signal that reaches the recording amplifier. The passive network is formed by the interaction between the passive tissue properties and the double-layer capacitance of electrodes. We show that it is possible to generate different electrograms by the change of the model parameters and that both the MAP and intermediate forms reside on a continuum of signals. Our model helps to decipher the mechanisms of signal generation and can lead to a better design for electrodes, recording amplifiers, and experimental setups. SIGNIFICANCERecording the Monophasic Action Potential (MAP) is potentially very useful in both experimental and clinical cardiac electrophysiology and can provide valuable information about the repolarization phase of the action potential. However, despite its benefits, it currently has only a small and niche role. The main challenge is the technical difficulties of recording an ideal MAP. Our results provide a better understanding of the mechanisms of the generation of cardiac electrograms and may help to optimize experiments and improve tools to achieve the full potentials of recording the MAP signals.

biophysics↗

Osteocyte death and bone overgrowth in mice lacking Fibroblast Growth Factor Receptors 1 and 2 in mature osteoblasts and osteocytes

Fibroblast Growth Factor (FGF) signaling pathways have well established roles in skeletal development, with essential functions in both chondrogenesis and osteogenesis. In mice, previous conditional knockout studies suggested distinct roles for FGF receptor 1 (FGFR1) signaling at different stages of osteogenesis and a role for FGFR2 in osteoblast maturation. However, the potential for redundancy among FGFRs and the mechanisms and consequences of stage-specific osteoblast lineage regulation were not addressed. Here, we conditionally inactivate Fgfr1 and Fgfr2 in mature osteoblasts with an Osteocalcin-Cre or Dentin matrix protein 1-CreER driver. We find that young mice lacking both receptors or only FGFR1 are phenotypically normal. However, after 6 weeks of age these Fgfr1/Fgfr2 double- and Fgfr1 single-conditional knockout mice develop a high bone mass phenotype with increased periosteal apposition, increased endocortical woven bone with increased porosity, and biomechanical properties that reflect increased bone mass but impaired material properties. Histopathological and gene expression analyses show that this phenotype is preceded by a striking loss of osteocytes, and gradual activation of the Wnt/{beta}Catenin signaling pathway. These data identify a role for FGFR1 signaling in mature osteoblasts/osteocytes that is required for osteocyte survival during postnatal bone growth.

developmental biology↗