Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells

Title: Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells
Authors: Miragoli, M
Moshkov, A
Novak, P
Shevchuk, A
Nikolaev, VO
El-Hamamsy, I
Potter, CMF
Wright, P
Kadir, SHSA
Lyon, AR
Mitchell, JA
Chester, AH
Klenerman, D
Lab, MJ
Korchev, YE
Harding, SE
Gorelik, J
Item Type: Journal Article
Abstract: Cardiovascular diseases are complex pathologies that include alterations of various cell functions at the levels of intact tissue, single cells and subcellular signalling compartments. Conventional techniques to study these processes are extremely divergent and rely on a combination of individual methods, which usually provide spatially and temporally limited information on single parameters of interest. This review describes scanning ion conductance microscopy (SICM) as a novel versatile technique capable of simultaneously reporting various structural and functional parameters at nanometre resolution in living cardiovascular cells at the level of the whole tissue, single cells and at the subcellular level, to investigate the mechanisms of cardiovascular disease. SICM is a multimodal imaging technology that allows concurrent and dynamic analysis of membrane morphology and various functional parameters (cell volume, membrane potentials, cellular contraction, single ion-channel currents and some parameters of intracellular signalling) in intact living cardiovascular cells and tissues with nanometre resolution at different levels of organization (tissue, cellular and subcellular levels). Using this technique, we showed that at the tissue level, cell orientation in the inner and outer aortic arch distinguishes atheroprone and atheroprotected regions. At the cellular level, heart failure leads to a pronounced loss of T-tubules in cardiac myocytes accompanied by a reduction in Z-groove ratio. We also demonstrated the capability of SICM to measure the entire cell volume as an index of cellular hypertrophy. This method can be further combined with fluorescence to simultaneously measure cardiomyocyte contraction and intracellular calcium transients or to map subcellular localization of membrane receptors coupled to cyclic adenosine monophosphate production. The SICM pipette can be used for patch-clamp recordings of membrane potential and single channel currents. In conclusion, SICM provides a highly informative multimodal imaging platform for functional analysis of the mechanisms of cardiovascular diseases, which should facilitate identification of novel therapeutic strategies.
Issue Date: 16-Feb-2011
Date of Acceptance: 18-Jan-2011
ISSN: 1742-5662
Publisher: The Royal Society
Start Page: 913
End Page: 925
Journal / Book Title: Journal of the Royal Society Interface
Volume: 8
Issue: 60
Copyright Statement: © 2011 The Royal Society. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (
Sponsor/Funder: Biotechnology and Biological Sciences Research Council (BBSRC)
Biotechnology and Biological Sciences Research Cou
British Heart Foundation
Funder's Grant Number: C19021
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
scanning ion conductance microscopy
vascular disease
heart failure
Aorta, Thoracic
Cardiovascular Diseases
Myocytes, Cardiac
MD Multidisciplinary
General Science & Technology
Notes: keywords: Animals,Aorta,Cardiac,Cardiac: physiology,Cardiac: ultrastructure,Cardiovascular Diseases,Cardiovascular Diseases: pathology,Heart,Heart: physiology,Humans,Microscopy,Microscopy: instrumentation,Microscopy: methods,Myocytes,Thoracic,Thoracic: physiology,Thoracic: ultrastructure pmid: 21325316
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine
Faculty of Natural Sciences

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