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Lab web-page: http://www.cup.uni-muenchen.de/ph/aks/biel/Main/Biel
Contact: mbiel@cup.uni-muenchen.de
Lay Summary:
There is initial evidence that upregulation of ventricular HCN
('pacemaker') channels in diseased states, such as heart failure,
hypertrophy and hypertension, predisposes the heart with associated
arrhythmias. However, so far, exploration of the role HCN channels play
in abnormal cardiac excitation was hampered by the lack of
pharmacological tools and of suitable transgenic animal models. Our
project aims at addressing this important issue by (1) the generation
and analysis of transgenic mouse lines overexpressing HCN channels in
heart muscle and (2) the generation and analysis of mouse lines with
heart muscle-specific deletion of HCN channels.
Relevant Publications:
- Hoes E, Stieber J, Herrmann S, Feil S, Tybl E, Hofmann F, Feil R, Ludwig A. Tamoxifen-induced gene deletion in the cardiac conduction system. Journal of Molecular and Cellular Cardiology 2008/45:62-69.
- Biel M, Wahl-Schott C, Michalakis S & Zong X. Hyperpolarization-Activated Cation Channels: From Genes to Function. Physiol Rev 2009/89:847-885.
- Knaus A, Zong X, Beetz N, Jahns R, Lohse MJ, Biel M, Hein L. Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine. Circulation 2007/115(7):872-880. (Link)
- Wahl-Schott C, Baumann L, Cuny H, Eckert C, Griessmeier K & Biel M. Switching off caldium-dependent inactivation in L-type calcium channels by an autoinhibitory domain. Proceedings of the National Academy of Sciences 2006/103 (42) / 17 October:15657-15662. (Link)
- Mistrik P, Pfeifer A & Biel M. The enhancement of HCN channel instantaneous current facilitated by slow deactivation is regulated by intracellular chloride concentration. Pflugers Archiv European Journal of Physiology 2006/Sep 452 (6):718-727. (Link)
- Mistrik P, Mader R, Michalakis S, Weidinger M, Pfeifer A, Biel M. The murine HCN3 gene encodes a hyperpolarization-activated cation channel with slow kinetics and unique response to cyclic nucleotides. J Biol Chem 2005/280(29):27056-27061. (Link)
- Wahl-Schott C, Baumann L, Zong X, Biel M. An arginine residue in the pore region is a key determinant of chloride dependence in cardiac pacemaker channels. J Biol Chem 2005/280(14):13694-13700. (Link)
- Zong X, Eckert C, Yuan H, Wahl-Schott C, Abicht H, Fang L, Li R, Mistrik P, Gerstner A, Much B, Baumann L, Michalakis S, Zeng R, Chen Z, Biel M. A novel mechanism of modulation of hyperpolarization-activated cyclic nucleotide-gated channels by Src kinase. J Biol Chem 2005/280(40):34224-34232. (Link)
- Er F, Larbig R, Ludwig A, Biel M, Hofmann F, Beuckelmann DJ, Hoppe UC. Dominant-negative suppression of HCN channels markedly reduces the native pacemaker current I(f) and undermines spontaneous beating of neonatal cardiomyocytes. Circulation 2003/107(3):485-489. (Link)
- Much B, Wahl-Schott C, Zong X, Schneider A, Baumann L, Moosmang S, Ludwig A, Biel M. Role of subunit heteromerization and N-linked glycosylation in the formation of functional hyperpolarization-activated cyclic nucleotide-gated channels. J Biol Chem 2003/278(44):43781-43786. (Link)
- Stieber J, Thomer A, Much B, Schneider A, Biel M, Hofmann F. Molecular basis for the different activation kinetics of the pacemaker channels HCN2 and HCN4. J Biol Chem 2003/278(36):33672-33680. (Link)
- Stieber J, Herrmann S, Feil S, Loster J, Feil R, Biel M, Hofmann F, Ludwig A. The hyperpolarization-activated channel HCN4 is required for the generation of pacemaker action potentials in the embryonic heart. Proc Natl Acad Sci U S A 2003/100(25):15235-15240. (Link)
- Moosmang S, Stieber J, Zong X, Biel M, Hofmann F, Ludwig A. Cellular expression and functional characterization of four hyperpolarization-activated pacemaker channels in cardiac and neuronal tissues. Eur J Biochem 2001/268(6):1646-1652. (Link)
- Zong X, Stieber J, Ludwig A, Hofmann F, Biel M. A single histidine residue determines the pH sensitivity of the pacemaker channel HCN2. J Biol Chem 2001/276(9):6313-6319. (Link)
- Vaca L, Stieber J, Zong X, Ludwig A, Hofmann F, Biel M. Mutations in the S4 domain of a pacemaker channel alter its voltage dependence. FEBS Lett 2000/479(1-2):35-40. (Link)
- Ludwig A, Zong X, Stieber J, Hullin R, Hofmann F, Biel M. Two pacemaker channels from human heart with profoundly different activation kinetics. Embo J 1999/18(9):2323-2329. (Link)
- Moosmang S, Biel M, Hofmann F, Ludwig A. Differential distribution of four hyperpolarization-activated cation channels in mouse brain. Biol Chem 1999/380(7-8):975-980. (Link)
- Ludwig A, Zong X, Jeglitsch M, Hofmann F, Biel M. A family of hyperpolarization-activated mammalian cation channels. Nature 1998/393(6685):587-591. (Link)
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