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Generation of Murine Cardiac Pacemaker Cell Aggregates Based on ES-Cell-Programming in Combination with Myh6-Promoter-Selection
Published on: February 17, 2015
Recycling endosomes supply cardiac pacemaker channels for regulated surface expression.
Nadine Hardel1, Nadine Harmel, Gerd Zolles
1Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Cardiovascular Research
|March 11, 2008
Summary
Cardiac pacemaker channels (HCN2 and HCN4) are stored in recycling endosomes and transported to the cell surface via phospholipase D2 (PLD2). This process is stimulated by angiotensin II, regulating channel expression.
Area of Science:
- Cellular and Molecular Biology
- Cardiovascular Physiology
- Neuroscience
Background:
- Cellular excitability depends on ion channel type and number.
- Cardiac pacemaker channel surface expression may be regulated by transport, not just biosynthesis.
- Trafficking pathways and molecular control of these channels remain largely unknown.
Purpose of the Study:
- Investigate the endocytic trafficking pathways of hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels.
- Identify molecular mechanisms controlling HCN channel surface transport.
- Determine the role of recycling endosomes in HCN channel regulation.
Main Methods:
- Studied endocytic trafficking of HCN2 and HCN4 channels in various cell types (opossum kidney cells, neurons, cardiomyocytes).
- Utilized fluorescent protein and epitope tagging for channel visualization and tracking.
- Investigated the role of phospholipase D2 (PLD2) and angiotensin II in channel recycling.
Main Results:
- Internalized HCN2 and HCN4 channels are sorted to Rab11-positive recycling endosomes (ERC).
- HCN channel surface transport from ERC depends on active PLD2.
- Angiotensin II stimulates ERC trafficking of HCN4 channels, increasing surface expression independently of biosynthesis.
Conclusions:
- Recycling endosomes act as intracellular storage for HCN2 and HCN4 pacemaker channels.
- These endosomes are vital for maintaining homeostatic surface expression.
- They also facilitate rapid adaptation of surface expression in response to stimuli.
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