Bringing bioelectricity to light.

Any bilayer lipid membrane can support a membrane voltage. The combination of optical perturbation and optical readout of membrane voltage opens the door to studies of electrophysiology in a huge variety of systems previously inaccessible to electrode-based measurements. Yet, the application of optogenetic electrophysiology requires careful reconsideration of the fundamentals of bioelectricity. Rules of thumb appropriate for neuroscience and cardiology may not apply in systems with dramatically different sizes, lipid compositions, charge carriers, or protein machinery. Optogenetic tools are not electrodes; thus, optical and electrode-based measurements have different quirks. Here we review the fundamental aspects of bioelectricity with the aim of laying a conceptual framework for all-optical electrophysiology.

[1]  L. Goldstein,et al.  Biophysical challenges to axonal transport: motor-cargo deficiencies and neurodegeneration. , 2014, Annual review of biophysics.

[2]  H. Walden,et al.  The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder. , 2014, Annual review of biophysics.

[3]  Carlos J Bustamante,et al.  Mechanisms of cellular proteostasis: insights from single molecule approaches (226.3) , 2014, Annual review of biophysics.

[4]  Adam E Cohen,et al.  Temporal dynamics of microbial rhodopsin fluorescence reports absolute membrane voltage. , 2014, Biophysical journal.

[5]  D. Maclaurin,et al.  Flash Memory: Photochemical Imprinting of Neuronal Action Potentials onto a Microbial Rhodopsin , 2014, Journal of the American Chemical Society.

[6]  Hong Qian,et al.  Statistics and Related Topics in Single-Molecule Biophysics. , 2014, Annual review of statistics and its application.

[7]  V. Pieribone,et al.  Genetically Targeted Optical Electrophysiology in Intact Neural Circuits , 2013, Cell.

[8]  Dougal Maclaurin,et al.  Mechanism of voltage-sensitive fluorescence in a microbial rhodopsin , 2013, Proceedings of the National Academy of Sciences.

[9]  T. Knöpfel,et al.  Optogenetic reporters , 2013, Biology of the cell.

[10]  Leonardo Sacconi,et al.  Palette of fluorinated voltage-sensitive hemicyanine dyes , 2012, Proceedings of the National Academy of Sciences.

[11]  Vincent A. Pieribone,et al.  Single Action Potentials and Subthreshold Electrical Events Imaged in Neurons with a Fluorescent Protein Voltage Probe , 2012, Neuron.

[12]  Sébastien Granier,et al.  A new era of GPCR structural and chemical biology. , 2012, Nature chemical biology.

[13]  C. Akerman,et al.  Optogenetic silencing strategies differ in their effects on inhibitory synaptic transmission , 2012, Nature Neuroscience.

[14]  N. Demaurex,et al.  Regulation of the mitochondrial proton gradient by cytosolic Ca2+ signals , 2012, Pflügers Archiv - European Journal of Physiology.

[15]  Roger Y. Tsien,et al.  Optically monitoring voltage in neurons by photo-induced electron transfer through molecular wires , 2012, Proceedings of the National Academy of Sciences.

[16]  D. Maclaurin,et al.  Optical recording of action potentials in mammalian neurons using a microbial rhodopsin , 2011, Nature Methods.

[17]  Adam E. Cohen,et al.  Electrical Spiking in Escherichia coli Probed with a Fluorescent Voltage-Indicating Protein , 2011, Science.

[18]  G. Cline,et al.  Plasma membrane electron transport in pancreatic β-cells is mediated in part by NQO1. , 2011, American journal of physiology. Endocrinology and metabolism.

[19]  Liwei Lin,et al.  Quantum dot nano thermometers reveal heterogeneous local thermogenesis in living cells. , 2011, ACS nano.

[20]  L. Avigliano,et al.  Trans-plasma membrane electron transport in mammals: functional significance in health and disease. , 2011, Antioxidants & redox signaling.

[21]  Rafael Yuste,et al.  Imaging Voltage in Neurons , 2011, Neuron.

[22]  A. Terakita,et al.  Diversity and functional properties of bistable pigments , 2010, Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology.

[23]  Michael A. Henninger,et al.  High-Performance Genetically Targetable Optical Neural Silencing via Light-Driven Proton Pumps , 2010 .

[24]  O. Demin,et al.  Modeling of ATP–ADP steady‐state exchange rate mediated by the adenine nucleotide translocase in isolated mitochondria , 2009, The FEBS journal.

[25]  P. Sebban,et al.  The local electric field within phospholipid membranes modulates the charge transfer reactions in reaction centres. , 2009, Biochimica et biophysica acta.

[26]  A. Demchenko,et al.  Nanoscopic description of biomembrane electrostatics: results of molecular dynamics simulations and fluorescence probing. , 2009, Chemistry and physics of lipids.

[27]  David L. Kaplan,et al.  Role of Membrane Potential in the Regulation of Cell Proliferation and Differentiation , 2009, Stem Cell Reviews and Reports.

[28]  K. Deisseroth,et al.  eNpHR: a Natronomonas halorhodopsin enhanced for optogenetic applications , 2008, Brain cell biology.

[29]  Joseph A. Mindell,et al.  The Cl-/H+ antiporter ClC-7 is the primary chloride permeation pathway in lysosomes , 2008, Nature.

[30]  J. Tuszynski,et al.  Molecular and Cellular Biophysics , 2005 .

[31]  B. Salzberg,et al.  A mechanical spike accompanies the action potential in Mammalian nerve terminals. , 2007, Biophysical journal.

[32]  Alexander G. Volkov,et al.  Plant Electrophysiology: Theory and Methods , 2007 .

[33]  D. Clapham,et al.  Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel , 2006, Nature.

[34]  W. Catterall,et al.  Overview of Molecular Relationships in the Voltage-Gated Ion Channel Superfamily , 2005, Pharmacological Reviews.

[35]  Francisco Bezanilla,et al.  A hybrid approach to measuring electrical activity in genetically specified neurons , 2005, Nature Neuroscience.

[36]  K. Deisseroth,et al.  Millisecond-timescale, genetically targeted optical control of neural activity , 2005, Nature Neuroscience.

[37]  Michael Pusch,et al.  Chloride/proton antiporter activity of mammalian CLC proteins ClC-4 and ClC-5 , 2005, Nature.

[38]  Yasushi Okamura,et al.  Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor , 2005, Nature.

[39]  Jeremy F. Koscielecki,et al.  Optimization of protein-based volumetric optical memories and associative processors by using directed evolution , 2005 .

[40]  R. Bruinsma,et al.  Electrostatics and the assembly of an RNA virus. , 2004, Physical review. E, Statistical, nonlinear, and soft matter physics.

[41]  G. Haddad,et al.  Calcium and pH homeostasis in neurons during hypoxia and ischemia. , 2004, Cell calcium.

[42]  Chen Zhang,et al.  Calcium- and Dynamin-Independent Endocytosis in Dorsal Root Ganglion Neurons , 2004, Neuron.

[43]  Christopher Miller,et al.  Secondary active transport mediated by a prokaryotic homologue of ClC Cl- channels , 2004, Nature.

[44]  David E. Clapham,et al.  The mitochondrial calcium uniporter is a highly selective ion channel , 2004, Nature.

[45]  K. Chandy,et al.  Molecular Properties and Physiological Roles of Ion Channels in the Immune System , 2001, Journal of Clinical Immunology.

[46]  Dirk Roos,et al.  Oxidative killing of microbes by neutrophils. , 2003, Microbes and infection.

[47]  I. Booth Bacterial ion channels. , 2003, Genetic engineering.

[48]  Deri Morgan,et al.  The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels , 2003, Nature.

[49]  L. Loew,et al.  The effect of asymmetric surface potentials on the intramembrane electric field measured with voltage-sensitive dyes. , 2003, Biophysical journal.

[50]  Richard Nuccitelli,et al.  A role for endogenous electric fields in wound healing. , 2003, Current topics in developmental biology.

[51]  Chen Zhang,et al.  Ca2+-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons , 2002, Nature Neuroscience.

[52]  M. Sansom,et al.  Viral ion channels: structure and function. , 2002, Biochimica et biophysica acta.

[53]  Christopher Miller,et al.  A biological role for prokaryotic ClC chloride channels , 2002, Nature.

[54]  C. Zhang,et al.  Ca(2+)-independent but voltage-dependent secretion in mammalian dorsal root ganglion neurons. , 2002, Nature neuroscience.

[55]  Christina Cramer,et al.  Antibiotic Susceptibility Profiles ofEscherichia coli Strains Lacking Multidrug Efflux Pump Genes , 2001, Antimicrobial Agents and Chemotherapy.

[56]  R. Clarke The dipole potential of phospholipid membranes and methods for its detection. , 2001, Advances in colloid and interface science.

[57]  J O Bustamante,et al.  Electrical dimension of the nuclear envelope. , 2001, Physiological reviews.

[58]  M. Ward,et al.  Mitochondrial membrane potential and neuronal glutamate excitotoxicity: mortality and millivolts , 2000, Trends in Neurosciences.

[59]  M. Haas,et al.  The Na-K-Cl cotransporter of secretory epithelia. , 2000, Annual review of physiology.

[60]  M. Blaustein,et al.  Sodium/calcium exchange: its physiological implications. , 1999, Physiological reviews.

[61]  X. L. Zhou,et al.  Ion channels in microbes. , 1999, Methods in enzymology.

[62]  Gero Miesenböck,et al.  Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins , 1998, Nature.

[63]  Karl-Heinz Krause,et al.  Electron currents generated by the human phagocyte NADPH oxidase , 1998, Nature.

[64]  L M Loew,et al.  Membrane electric properties by combined patch clamp and fluorescence ratio imaging in single neurons. , 1998, Biophysical journal.

[65]  R. Clarke,et al.  Effect of lipid structure on the dipole potential of phosphatidylcholine bilayers. , 1997, Biochimica et biophysica acta.

[66]  F. L. Crane,et al.  Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[67]  Leslie M. Loew,et al.  Distinct electric potentials in soma and neurite membranes , 1994, Neuron.

[68]  R. Krämer,et al.  Functional properties of the reconstituted phosphate carrier from bovine heart mitochondria: evidence for asymmetric orientation and characterization of three different transport modes. , 1993, Biochimica et biophysica acta.

[69]  E. Padan,et al.  Proton-sodium stoichiometry of NhaA, an electrogenic antiporter from Escherichia coli. , 1993, The Journal of biological chemistry.

[70]  D. Luster,et al.  Plasma Membrane Redox Activity: Components and Role in Plant Processes , 1993 .

[71]  F. L. Crane,et al.  Requirement for coenzyme Q in plasma membrane electron transport. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[72]  W. Helfrich,et al.  Bending elasticity of electrically charged bilayers : coupled monolayers, neutral surfaces, and balancing stresses , 1992 .

[73]  A. Schmid,et al.  Voltage-dependent InsP3- insensitive calcium channels in membranes of pancreatic endoplasmic reticulum vesicles , 1990, Nature.

[74]  William E. Brownell,et al.  Outer Hair Cell Electromotility and Otoacoustic Emissions , 1990, Ear and hearing.

[75]  C. Bronner,et al.  Resting plasma membrane potential of rat peritoneal mast cells is set predominantly by the sodium pump , 1989, FEBS letters.

[76]  C Kung,et al.  Modified reconstitution method used in patch-clamp studies of Escherichia coli ion channels. , 1989, Biophysical journal.

[77]  S. McLaughlin,et al.  The electrostatic properties of membranes. , 1989, Annual review of biophysics and biophysical chemistry.

[78]  W. Helfrich,et al.  Effect of surface charge on the curvature elasticity of membranes , 1988 .

[79]  C Kung,et al.  Pressure-sensitive ion channel in Escherichia coli. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[80]  C. Kung,et al.  Ion channels in yeast. , 1986, Science.

[81]  D. Malchow,et al.  Single ion channels in the slime mold Dictyostelium discoideum. , 1986, Biochimica et biophysica acta.

[82]  C. L. Bashford,et al.  Plasma membrane potential of some animal cells is generated by ion pumping, not by ion gradients , 1986 .

[83]  F. L. Crane,et al.  Transplasma-membrane redox systems in growth and development. , 1985, Biochimica et biophysica acta.

[84]  K. Chandy,et al.  A voltage‐gated potassium channel in human T lymphocytes. , 1985, The Journal of physiology.

[85]  P. Fleming,et al.  Cytochrome b561 catalyzes transmembrane electron transfer. , 1984, The Journal of biological chemistry.

[86]  M. Seeds,et al.  Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. , 1983, Journal of immunology.

[87]  H. Sies,et al.  Mitochondrial and cytosolic ATP/ADP ratios in rat liver in vivo. , 1981, The Biochemical journal.

[88]  C. Slayman,et al.  Role of the plasma membrane proton pump in pH regulation in non-animal cells. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[89]  A. Eddy,et al.  The accumulation of amino acids by mouse ascites-tumour cells. Dependence on but lack of equilibrium with the sodium-ion electrochemical gradient. , 1981, The Biochemical journal.

[90]  C. Slayman,et al.  Quantitative measurements of membrane potential in Escherichia coli. , 1980, Biochemistry.

[91]  J. Hoffman,et al.  The relation between dicarbocyanine dye fluorescence and the membrane potential of human red blood cells set at varying Donnan equilibria , 1979, The Journal of general physiology.

[92]  S. Schultz,et al.  Sodium-coupled chloride transport by epithelial tissues. , 1979, The American journal of physiology.

[93]  S. McLaughlin Electrostatic Potentials at Membrane-Solution Interfaces , 1977 .

[94]  J. Hoffman,et al.  Determination of membrane potentials in human and Amphiuma red blood cells by means of a fluorescent probe , 1974, The Journal of physiology.

[95]  R. Keynes,et al.  ELECTROGENIC ION PUMPS , 1974, Annals of the New York Academy of Sciences.

[96]  P. Muir Wood The redox potential of the system oxygen--superoxide. , 1974, FEBS letters.

[97]  H. Saddler,et al.  The Membrane Potential of Acetabularia mediterranea , 1970, The Journal of general physiology.

[98]  A. Maroudas,et al.  Physicochemical properties of cartilage in the light of ion exchange theory. , 1968, Biophysical journal.

[99]  P. Mitchell CHEMIOSMOTIC COUPLING IN OXIDATIVE AND PHOTOSYNTHETIC PHOSPHORYLATION , 1966, Biological reviews of the Cambridge Philosophical Society.

[100]  C. Slayman Electrical Properties of Neurospora crassa Respiration and the intracellular potential , 1965 .

[101]  Werner R. Loewenstein,et al.  Some Electrical Properties of a Nuclear Membrane Examined with a Microelectrode , 1963, The Journal of general physiology.

[102]  A. Hodgkin,et al.  The influence of potassium and chloride ions on the membrane potential of single muscle fibres , 1959, The Journal of physiology.

[103]  K. Burton,et al.  The free-energy changes for the reduction of diphosphopyridine nucleotide and the dehydrogenation of L-malate and L-glycerol 1-phosphate. , 1953, The Biochemical journal.

[104]  J. Burdon-Sanderson I. Note on the electrical phenomena which accompany irritation of the leaf of Dionæa muscipula , 1873, Proceedings of the Royal Society of London.