title: A role for membrane shape and information processing in cardiac physiology.
abstract: While the heart is a dynamic organ and one of its major functions is to provide the organism with sufficient blood supply, the regulatory feedback systems, which allow adaptation to hemodynamic changes, remain not well understood. Our current description of mechanosensation focuses on stretch-sensitive ion channels, cytoskeletal components, structures such as the sarcomeric Z-disc, costameres, caveolae, or the concept of tensegrity, but these models appear incomplete as the remarkable plasticity of the myocardium in response to biomechanical stress and heart rate variations remains unexplained. Signaling activity at membranes depends on their geometric parameters such as surface area and curvature, which links shape to information processing. In the heart, continuous cycles of contraction and relaxation reshape membrane morphology and hence affect cardio-mechanic signaling. This article provides a brief review on current models of mechanosensation and focuses on how signaling, cardiac myocyte dynamics, and membrane shape interact and potentially give rise to a self-organized system that uses shape to sense the extra- and intracellular environment. This novel concept may help to explain how changes in frequency, and thus membrane shape, affect cardiac plasticity. One of the conclusions is that hypertrophy and associated fibrosis, which have been considered as necessary to cope with increased wall stress, can also be seen as part of complex feedback systems which use local membrane inhomogeneity in different cardiac cell types to influence whole organphysiology and which are predicted to fine-tune and thus regulate membrane-mediated signaling.
authors.affiliation: Innovative Medicines and Early Development, Cardiovascular and Metabolic Diseases iMed, AstraZeneca Research and Development Mölndal, Pepparedsleden 1, SE-431 83, Mölndal, Sweden, ralph.knoell@astrazeneca.com.
authors.forename: Ralph
authors.initials: R
authors.lastname: Knöll
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology*; D056966:Excitation Contraction Coupling / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008560:Membrane Fluidity / Q000502:physiology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000502:physiology*