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Storch Lab: Ca2+ Permeable Cation Channels

Head: Dr. Ursula Storch

Coworkers: Moira Mager, cand. med.

German - AG Storch

My group is investigating unselective, calcium permeable ion channels of the “transient receptor potential“ (TRP) channel family with focus on the classical or canonical TRP channels (TRPCs) which are receptor-operated and are activated by G-protein coupled receptors via phospholipase C activation without the involvement of protein kinase C.

We are mainly interested in the biophysical and functional characterization of TRP channels. To analyze the physiological role of these channels several gene-deficient mouse models are available at the institute. Moreover, we are interested in mechanosensation and –transduction of vascular smooth muscle cells from resistance arteries which are essential for myogenic vasoconstriction or Bayliss effect and of podocytes which are critically involved in nephropathies leading to renal failure. In Germany, diabetic nephropathy is the main cause for total renal failure requiring dialysis. To analyze the pathomechanism of nephropathy in more detail a mouse model for type 2 diabetes is available.

In particular, we are analyzing the mechanosensory or –transduction properties of G-protein coupled receptors like the mechanosensitive angiotensin II AT1 receptors and of ion channels. For this, we use electrophysiological patch-clamp measurements in the whole-cell and single-cell configuration, fluorimetric calcium and manganese quenching experiments with fura-2, molecular biology and biochemistry. Moreover, myogenic tone of isolated small resistance arteries ex vivo is determined performing pressure myography.

The aim of our research is the identification and functional characterization of ion channels and G-protein coupled receptors involved in physiology and pathophysiology which might help to identify new targets for pharmaceuticals.

Publikationen Ursula Storch

Original Papers

1. Forst AL, Olteanu VS, Mollet G, Wlodkowski T, Schaefer F, Dietrich A, Reiser, J, Gudermann T, Mederos y Schnitzler M and Storch U.
Podocyte purinergic P2X4 channels are mechanotransducers that mediate cytoskeletal disorganization.
J Am Soc Nephrol. 2016 Mar; 27(3):848-62.

2. Kalwa H, Storch U, Demleitner J*, Fiedler S, Mayer T, Kannler M, Fahlbusch M, Barth H, Smrcka A, Hildebrandt F, Gudermann T and Dietrich A.
Phospholipase C epsilon-induced TRPC6 activation: A common but redundant mechanism in primary podocytes.
J Cell Physiol. 2015 Jun;230(6):1389-99

3. Storch U, Blodow S, Gudermann T and Mederos y Schnitzler M.
Cysteinyl Leukotriene 1 receptors as novel mechanosensors mediating myogenic tone together with angiotensin II type 1 receptors.
Arterioscler Thromb Vasc Biol. 2015 Jan;35(1):121-6.

4. Malczyk M, Veith C, Fuchs B, Hofmann K, Storch U, Schermuly RT, Witzenrath M, Ahlbrecht K, Fecher-Trost C, Flockerzi V, Ghofrani HA, Grimminger F, Seeger W, Gudermann T, Dietrich A and Weissmann N.
Classical transient receptor potential channel 1 in hypoxia-induced pulmonary hypertension.
Am J Respir Crit Care Med. 2013 Dec 15;188(12):1451-9.

5. Blodow S, Schneider H, Storch U, Wizemann R, Forst AL, Gudermann T and Mederos y Schnitzler M.
Novel role of mechanosensitive AT1B receptors in myogenic vasoconstriction. Pflugers Arch. 2014 Jul;466(7):1343-53.

6. Weissmann N, Sydykov A, Kalwa H, Storch U, Fuchs B, Mederos y Schnitzler M, Brandes RP, Grimminger F, Meissner M, Freichel M, Offermanns S, Veit F, Pak O, Krause KH, Schermuly RT, Brewer AC, Schmidt HH, Seeger W, Shah AM, Gudermann T, Ghofrani HA and Dietrich A.
Activation of TRPC6 channels is essential for lung ischaemia-reperfusion induced oedema in mice.
Nat Commun. 2012 Jan 31;3:649

7. Jung CB, Moretti A, Mederos y Schnitzler M, Iop L, Storch U, Bellin M, Dorn T, Ruppenthal S, Pfeiffer S, Goedel A, Dirschinger RJ, Seyfarth M, Lam JT, Sinnecker D, Gudermann T, Lipp P and Laugwitz KL.
Dantrolene rescues arrhythmogenic RYR2 defect in a patient-specific stem cell model of catecholaminergic polymorphic ventricular tachycardia.
EMBO Mol Med. 2012 Mar;4(3):180-91.

8. Storch U, Forst AL, Philipp M, Gudermann T and Mederos y Schnitzler M.
Transient receptor potential channel 1 (TRPC1) reduces calcium permeability in heteromeric channel complexes.
J Biol Chem. 2012 Jan 27;287(5):3530-40.

9. Mederos y Schnitzler M, Storch U, Meibers S, Nurwakagari P, Breit A, Essin K, Gollasch M and Gudermann T.
Gq-coupled receptors as mechanosensors mediating myogenic vasoconstriction.
EMBO J. 2008 Dec 3;27(23):3092-103.

10. Dietrich A, Kalwa H, Storch U, Mederos y Schnitzler M, Salanova B, Pinkenburg O, Dubrovska G, Essin K, Gollasch M, Birnbaumer L and Gudermann T.
Pressure-induced and store-operated cation influx in vascular smooth muscle cells is independent of TRPC1.
Pflugers Arch. 2007 Dec;455(3):465-77. Epub 2007 Jul 24.

11. Weissmann N, Dietrich A, Fuchs B, Kalwa H, Ay M, Dumitrascu R, Olschewski A, Storch U, Mederos y Schnitzler M, Ghofrani HA, Schermuly RT, Pinkenburg O, Seeger W, Grimminger F and Gudermann T.
Classical transient receptor potential channel 6 (TRPC6) is essential for hypoxic pulmonary vasoconstriction and alveolar gas exchange.
Proc Natl Acad Sci U S A. 2006 Dec 12;103(50):19093-8.

12. Dietrich A, Mederos Y Schnitzler M, Gollasch M, Gross V, Storch U, Dubrovska G, Obst M, Yildirim E, Salanova B, Kalwa H, Essin K, Pinkenburg O, Luft FC, Gudermann T and Birnbaumer L.
Increased vascular smooth muscle contractility in TRPC6-/- mice.
Mol Cell Biol. 2005 Aug;25(16):6980-9.

Reviews

1. Mederos y Schnitzler M, Storch U, and Gudermann T.
Mechanosensitive Gq/11 -protein coupled receptors mediate myogenic vasoconstriction.
Microcirculation. 2016 Jun 25. doi: 10.1111/micc.12293.

2. Storch U, Mederos y Schnitzler M and Gudermann T.
G protein-mediated stretch reception.
Am J Physiol Heart Circ Physiol. 2012 Mar 15;302(6):H1241-9.

3. Mederos y Schnitzler M, Storch U, and Gudermann T.
AT1 receptors as mechanosensors.
Curr Opin Pharmacol. 2011 Apr;11(2):112-6.

4. Dietrich A, Mederos y Schnitzler M, Kalwa H, Storch U, and Gudermann T.
Functional characterization and physiological relevance of the TRPC3/6/7 subfamily of cation channels.
Naunyn Schmiedebergs Arch Pharmacol. 2005 Apr;371(4):257-65.