The Impact of Heterozygous Mutations Associated With Pulmonary Arterial Hypertension on Channel Function and Pharmacological Recovery.

Background: Heterozygous loss of function mutations in the gene cause hereditary pulmonary arterial hypertension (PAH). encodes an acid-sensitive potassium channel, which contributes to the resting potential of human pulmonary artery smooth muscle cells. KCNK3 is widely expressed in the body, and dimerizes with other KCNK3 subunits, or the closely related, acid-sensitive KCNK9 channel.

Directed Differentiation of Human Pluripotent Stem Cells to Microglia.

Microglia, the immune cells of the brain, are crucial to proper development and maintenance of the CNS, and their involvement in numerous neurological disorders is increasingly being recognized. To improve our understanding of human microglial biology, we devised a chemically defined protocol to generate human microglia from pluripotent stem cells. Myeloid progenitors expressing CD14/CX3CR1 were generated within 30 days of differentiation from both embryonic and induced pluripotent stem cells (iPSCs).

Contributions of bone morphogenetic proteins in cardiac repair cells in three-dimensional in vitro models and angiogenesis.

One of the main efforts in myocardial tissue engineering is towards designing cardiac tissues able to rescue the reduction in heart function once implanted at the site of myocardial infarction. To date, the efficiency of this approach in preclinical applications is limited in part by our incomplete understanding of the inflammatory environment known to be present at the site of myocardial infarct and by poor vascularization. It was recently reported that polarized macrophages known to be present at the site of myocardial infarction secrete bone morphogenetic proteins (BMPs)-2 and -4 causing changes in the expression of cardiac proteins in a 2D in vitro model.

Molecular Pathophysiology of Congenital Long QT Syndrome.

Ion channels represent the molecular entities that give rise to the cardiac action potential, the fundamental cellular electrical event in the heart. The concerted function of these channels leads to normal cyclical excitation and resultant contraction of cardiac muscle. Research into cardiac ion channel regulation and mutations that underlie disease pathogenesis has greatly enhanced our knowledge of the causes and clinical management of cardiac arrhythmia.

Dynamic subunit stoichiometry confers a progressive continuum of pharmacological sensitivity by KCNQ potassium channels.

Voltage-gated KCNQ1 (Kv7.1) potassium channels are expressed abundantly in heart but they are also found in multiple other tissues. Differential coassembly with single transmembrane KCNE beta subunits in different cell types gives rise to a variety of biophysical properties, hence endowing distinct physiological roles for KCNQ1-KCNEx complexes.