The aim of our research is to determine how mechanical stimulus is converted to electrical activity or metabolic changes in different cell types, and how different ion channels participate in this process.
Mechanosensitivity is found in almost every cell in all organisms, from bacteria to vertebrates, and covers a wide spectrum of functions from osmosensing to specialised organs like the skin receptors, hair cells in hearing organs or muscle receptors important for proper motor function.
Since most development regarding the molecular aspects of the mechanosensitive ion channel (MSC) has been made in non-sensory systems, it is important to also focus on mechanosensitivity of sensory organs where the functional importance is undisputed. In our research we analyse the stretch receptor organ of the crustaceans; a muscle receptor analogous to the human muscle spindle using electrophysiological and molecular techniques.
The receptor organ contains two receptors; one slowly adaptive, and one rapidly adaptive receptor neuron. The primary mechanosensitivity is generated by two MSC of hitherto unknown molecular type. The sensory neurones also contain voltage gated ion channels which contribute to the overall function of the receptor neurones.
Together with other groups we also study other cell types involved in osmosensing and the ion channels responsible for this. We also cooperate with other departments in analysing intestinal mucosal cells.
Sensory transduction and ion channels in mechanosensory cells
In this project we try to define the mechanosensory ion channels in the stretch receptor neurons of the crayfish using PCR technique. We also study the Na+- and K+ channels which contribute to the overall function of the sensory neurons. We are currently working along different lines:
- analysis of the Na+-permeability system in the receptors using two microelectrode- and patch clamp techniques
- analysis of different K+ channels including Ca2+ dependent K+ channels
- spatial distribution of Na+ and K+ channels and the consequences for the adaptation
Studies of human intestinal epithelial cells
In this project intestinal cells from colonic mucosa have been studied. Different ion channels important for ion and solute transport is being analysed using the patch clamp technique. We are currently trying to see if it is possible to use this technique on duodenal mucosal cells.
The first goal will be to establish primary culture of these cells. The project is carried out in cooperation with the Department of Molecular Medicine and Surgery.
Vagal sensory fibres: activity and function
In this project vagal afferent activity is analysed in relation to gastric function. The effect of different intestinal hormones on the vagal afferents and their receptors is studied using extracellular recordings from the vagal nerve and molecular techniques.
Thyroid hormone receptor alpha can control action potential duration in mouse ventricular myocytes through the KCNE1 ion channel subunit.
Acta Physiol (Oxf) 2010 Feb;198(2):133-42
Ion channels for mechanotransduction in the crayfish stretch receptor
MECHANOSENSITIVE ION CHANNELS, PT B 59: 21-48, 2007
Hypotonic stress activates an intermediate conductance K+ channel in human colonic crypt cells.
Acta Physiol. Scand. 2004 Dec;182(4):361-8
Different spatial distributions of sodium channels in the slowly and rapidly adapting stretch receptor neuron of the crayfish.
Brain Res. 1999 Jun;830(2):353-7
Local anaesthetics potentiate GABA-mediated Cl- currents by inhibiting GABA uptake.
Neuroreport 1997 Jan;8(2):465-8
Carbachol induces oscillations in membrane potential and intracellular calcium in a colonic tumor cell line, HT-29.
Am. J. Physiol. 1997 Oct;273(4 Pt 1):C1186-93
A mathematical model of the crustacean stretch receptor neuron. Biomechanics of the receptor muscle, mechanosensitive ion channels, and macrotransducer properties.
J. Neurophysiol. 1996 Oct;76(4):2211-20
A light emitting diode microspectrophotometer: intracellular Ca2+ measurements in isolated stretch receptor.
J. Neurosci. Methods 1993 Jun;48(1-2):43-50
Transducer properties of the rapidly adapting stretch receptor neurone in the crayfish (Pacifastacus leniusculus).
J. Physiol. (Lond.) 1993 Sep;469():193-211
Crayfish stretch receptor: an investigation with voltage-clamp and ion-sensitive electrodes.
J. Physiol. (Lond.) 1978 Nov;284():155-79