Investigation of IKs and IKr modulation by adrenergic signaling pathways in transgenic mouse models
O. Pongs, ZMNH,
Institute of Neuronal Signal TransductionContact:
pointuri@uke.uni-hamburg.de
Objectives
- Do mutant IKr or IKs channels affect the QT interval in electrocardiograms of mice?
- Are mutant IKr or IKs channels, which do not respond in vitro to cAMP or PI(4,5)P2, insensitive to adrenergic stimulation in vivo?
- Does adrenergic stimulation of mutant IKr or IKs channels in vivo require accessory proteins like AKAPs and 14-3-3ε?
- Do the mouse mutants develop life-threatening tachycardias under physical and/or emotional stress?
Selected references
- Plüger S, Faulhaber J, Furstenau M, Löhn M, Waldschütz R, Gollasch M, Haller H, Luft H-C, Ehmke H, Pongs, O (2000) Mice with disrupted BK channel #1 subunit gene feature abnormal Ca2+ Spark/STOC coupling and elevated blood pressure. Circ. Res. 87, E53-60
- Bähring R, Milligan CJ, Vardanyan V, Engeland B, Young BA, Dannenberg J, Waldschütz R, Edwards JP, Wray D, Pongs O (2001) Coupling of voltage-dependent potassium-channel inactivation and oxidoreductase active site of Kv# subunits. J Biol Chem 276, 22923-22929
- Wedekind H, Hauenschild S, Schwarz M, Isbrandt D, Djonlagic H, Wülfing T, Pongs O, Breithardt G, Haferkamp W, Schulze-Bahr E (2004) Long-term follow-up of a family with Romano-Ward syndrome and two KCNQ1 mutations located in cis. Clin Genet 65, 233-241
- Sinneger-Brauns MJ, Hetzenauer A, Huber IG, Renström E, Wietzorrek G, Berjukov S, Cavalli M, Walter D, Waldschütz R, Hering S, Bova S, Rorsman P, Pongs O, Singewald N, Striessnig J (2004) Cav1.3 L-type calciuM-channels: role for isoform-specific regulation of mood behavior, pancreatic beta-cell and cardiovascular function. J Clin Invest 113, 1430-1439
- Peters HC, Hu H, Pongs O, Storm JF, D Isbrandt (2005) Conditional transgenic suppression of M-channels in mouse brain reveals functions in neuronal excitability, resonance and behavior. Nature Neurosci 8, 51-60
