Our research projects are directed towards understanding the mechanism of contraction and its regulation in muscle cells.
Muscle contraction is a key event in several physiologically important processes, e.g. the movement of the legs during running, and control of blood pressure by contraction of vessels and the beating of the heart.
Research in our laboratory
Our research focus is mainly on smooth and cardiac muscle, two muscle types that are involved in several pathological conditions in humans. We are currently exploring processes involved in cellular signaling in smooth muscle, mainly regulation of myosin phosphatase by Rho-Rho kinase and protein kinase C pathways, using preparations from intestine, urinary bladder, urethra, blood vessels and airways.
The processes involved in regulation of cardiac contraction are examined using recordings of contraction and of electrophysiological properties of isolated cardiomyocytes and trabecular preparations. The studies of isolated cardiac tissue are combined with measurements using perfused whole heart preparations (Langendorff technique) and with structural characterization using small angle X-ray diffraction at the HASY-lab synchrotron radiation beamline, Hamburg.
Cellular signalling in smooth muscle
The aim is to elucidate the processes modulating the Ca2+-sensitivity of smooth muscle contraction, mainly protein kinase C and Rho-kinase. Intact and permeabilized preparations are used together with organ culture techniques and transfection of specific genes. Several unique knock-out and transgenic animal models are used.
Contractile mechanism in cardiac muscle
The regulation and mechanism of cardiac contraction are studied in animals (mice) with alterations in membrane and cytoskeletal proteins. The analysis is performed in whole animals using ECG and echocardiography and in isolated tissue using perfused whole hearts and isolated trabecular preparations.
Effects of inflammation and infection on urinary bladder contraction
Cellular signalling in smooth muscle and urothelium involved in the altered bladder contractility following urinary tract infection is examined in experiments with bacterial preparations and uropathogenic bacteria on isolated urinary bladder preparations.
- In vitro studies of contractility in isolated muscle preparations (skeletal, cardiac and smooth), including microvessel preparations
- Skinned (permeabilized) muscle preparations
- Caged-compound technology to photolytically release ATP, Ca2+ and transmitters
- Measurement of intracellular [Ca2+] with indicators (e.g. Fura-2 and calcium green)
- Organ culture methods for smooth muscle preparations
- Biochemical analysis of smooth muscle (SDS-PAGE, Western blot)
- Confocal micropscopy (Zeiss M510 Meta)
- X-ray diffraction of muscle fibre preparations
- Langendorff isolated beating heart preparations
- Electrophysiology, patch-clamp and Ca2+ measurements on isolated cardiomyocytes
- Telemetry ECG, body temperature, activity and blood pressure in living awake mice
- Blood pressure (artery and vein catheterization)
- Echocardiography (cardiac ultrasound examination)
- Open circuit calorimetry (Columbus system) for determination of whole mouse metabolism
- Mouse cystometry
- Several animal models for smooth muscle adaptation/growth in vivo
- Swedish Research Council
- Swedish Heart-Lung Foundation
- Karolinska Institutet
- Ragnar Söderberg's Foundation (site in Swedish)
- Pfizer-Karolinska Institutet collaborative grants