Table Of Content

General Physiology is the study of biological mechanisms through analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance Vol 139 ¢ No 1 @ January 2012 Commentaries 1 Model-free free energy for voltage-gated channels. Christopher Miller Articles 3 Estimating the voltage-dependent free energy change of ion channels using the median voltage for activation. Sandipan Chowdhury and Baron Chanda 19 The light-sensitive conductance of melanopsin-expressing Joseph and Hesse cells in amphioxus. Camila Pulido, Gerardo Malagon, Camilo Ferrer, Jun Kui Chen, Juan Manuel Angueyra, Enrico Nasi, and Maria del Pilar Gomez 31 Speed, adaptation, and stability of the response to light in cone photoreceptors: The functional role of Ca-dependent modulation of ligand sensitivity in cGMP-gated ion channels. Juan |. Korenbrot 57 An extracellular domain of the accessory 81 subunit is required for modulating BK channel voltage sensor and gate. Aleksandra Gruslova, lurii Semenov, and Bin Wang 69 Mechanism of inhibition of connexin channels by the quinine derivative N-benzylquininium. Clio Rubinos, Helmuth A. Sanchez, Vytas K. Verselis, and Miduturu Srinivas Tutorial Research Articles 83 Light inactivation of water transport and protein-protein interactions of aquaporin-Killer Red chimeras. Florian Baumgart, Andrea Rossi, and A.S. Verkman Journal Club 93 Co-transmission of dopamine and glutamate. John |. Broussard Cover picture: Light exposure (chromophore-assisted light inactivation [CALI]) destroys aquaporin-4 (AQP4) water channels in an AQP4-Killer Red (KR) chimera. A neuromyelitis optica AQP4 autoantibody (NMO-IgG, green) binds to AOP4 in cell mem- branes. After AQP4 destruction by CALI, NMO-IgG binding is greatly reduced. As a control, NMO-IgG binding is not reduced when KR is expressed in cytoplasm rather than conjugated to AOP4 (see tutorial research article by Baumgart et al., 83-91). General Physiology is the study of biological mechanisms eon analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance. Vol 139 © No 2 ¢ February 2012 Commentaries 97 Tilting and twirling as myosin V steps along actin filaments as detected by fluorescence polarization. David M. Warshaw Articles 101 The azimuthal path of myosin V and its dependence on lever-arm length. John H. Lewis, John F. Beausang, H. Lee Sweeney, and Yale E. Goldman 121 Apical Ca**-activated potassium channels in mouse parotid acinar cells. Janos Almassy, Jong Hak Won, Ted B. Begenisich, and David |. Yule 135 Characterization of KCNQ1 atrial fibrillation mutations reveals distinct dependence on KCNE1. Priscilla J. Chan, Jeremiah D. Osteen, Dazhi Xiong, Michael S. Bohnen, Darshan Doshi, Kevin J. Sampson, Steven O. Marx, Arthur Karlin, and Robert S. Kass lon selectivity and current saturation in inward-rectifier K* channels. Lei Yang, Johan Edvinsson, Henry Sackin, and Lawrence G. Palmer Functional significance of the taper of vertebrate cone photoreceptors. Ferenc|. Harosi and Ihigo Novales Flamarique Cover picture: An individual myosin V, labeled with a bifunctional rhodamine probe at fixed angle, Op, dp on its lever arm (top, no. 2) and stepping on actin, is analyzed by polarized total internal reflection microscopy (bottom). Time-resolved probe orientations are initially measured in a laboratory coordinate frame (bottom) and transformed into an actin frame (top, no. 1), giving probe angles Bp, ap. A novel analysis allowed Lewis et al. to determine Op, dp in the lever frame (top, no. 2), which is used with measured probe angles, Bp, ap, to calculate the physiologically relevant lever orientations, ,, a, (top, no. 3; see article by Lewis et al., 101-120). General Physiology is the study of biological mechanisms decudl analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance. Vol 139 © No 3 © March 2012 Articles 189 Properties of Ca** sparks revealed by four-dimensional confocal imaging of cardiac muscle. Vyacheslav M. Shkryl, Lothar A. Blatter, and Eduardo Rios 209 Sarcoplasmic reticulum Ca** permeation explored from the lumen side in mdx muscle fibers under voltage control. Gaélle Robin, Christine Berthier, and Bruno Allard 219 Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Ca,2.3 calcium channels. Aleksandr Shcheglovitov, luliia Vitko, Roman M. Lazarenko, Peihan Orestes, Slobodan M. Todorovic, and Edward Perez-Reyes Selectivity filter gating in large-conductance Ca**-activated K* channels. Jill Thompson and Ted Begenisich Revisiting inward rectification: K ions permeate through Kir2.1 channels during high-affinity block by spermidine. Tai-An Liu, Hsueh-Kai Chang, and Ru-Chi Shieh Cover picture: An average (n = 150) cardiac myocyte Ca** spark in “4-D.” Each row shows 2-D images (xy) at three vertical (z) positions separated by 1 ym; each column shows the spark at different times, separated by an interval of 5.6 ms. During the rise time (first four rows), the right-most image is the largest, as it was acquired last. The opposite is true during the decay phase. This feature was used to establish that each spark used in the average was in focus (see article by Shkryl et al., 189-207). General Physiology is the study of biological mechanisms Seu analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance. Vol 139 ¢ No 4 # April 2012 Brief Reviews 261 Intracellular calcium movements during excitation—contraction coupling in mammalian slow-twitch and fast-twitch muscle fibers. Stephen M. Baylor and Stephen Hollingworth Articles 273 Selective disruption of high sensitivity heat activation but not capsaicin activation of TRPV1 channels by pore turret mutations. Yuanyuan Cui, Fan Yang, Xu Cao, Vladimir Yarov-Yarovoy, KeWei Wang, and Jie Zheng 285 The voltage dependence of the TMEM16B/anoctamin2 calcium-activated chloride channel is modified by mutations in the first putative intracellular loop. Valentina Cenedese, Giulia Betto, Fulvio Celsi, O. Lijo Cherian, Simone Pifferi, and Anna Menini Tuning the tetraethylammonium sensitivity of potassium channel Kcv by subunit combination. Qiulin Tan, Brandon Ritzo, Kai Tian, and Li-Qun Gu Scorpion B-toxin interference with Nay channel voltage sensor gives rise to excitatory and depressant modes. Enrico Leipold, Adolfo Borges, and Stefan H. Heinemann Cover picture: The TRPV1 channel's pore turret is important for heat-induced activation. Changes in the turret sequence (top left) do not cause major changes in the protein's targeting to the plasma membrane (bottom left) nor to its sensitivity to capsaicin (bottom right). However, heat-induced activation was significantly altered (top right), suggesting a specific role for the turret in heat activation (see article by Cui et al., 273-283). General Physiology is the study of biological mechanisms dwoush analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance. Vol 139 © No 5 e May 2012 Articles 321 Inorganic polyphosphate is a potent activator of the mitochondrial permeability transition pore in cardiac myocytes. Lea K. Seidimayer, Maria R. Gomez-Garcia, Lothar A. Blatter, Evgeny Pavlov, and Elena N. Dedkova 333 Gating properties of the P2X2a and P2X2b receptor channels: Experiments and mathematical modeling. Anmar Khadra, Zonghe Yan, Claudio Coddou, Melanija Tomi¢, Arthur Sherman, and Stanko S. Stojilkovic 349 The intrinsic energy of the gating isomerization of a neuromuscular acetylcholine receptor channel. Tapan K. Nayak, Prasad G. Purohit, and Anthony Auerbach 359 Identification of a novel post-hydrolytic state in CFTR gating. Kang-Yang Jih, Yoshiro Sohma, Min Li, and Tzyh-Chang Hwang Tutorial Research Article 371 Analysis of high-affinity assembly for AMPA receptor amino-terminal domains. Huaying Zhao, Anthony J. Berger, Patrick H. Brown, Janesh Kumar, Andrea Balbo, Carrie A. May, Ernesto Casillas Jr., Thomas M. Laue, George H. Patterson, Mark L. Mayer, and Peter Schuck Corrections 389 Molecular and biophysical basis of glutamate and trace metal modulation of voltage-gated Ca,2.3 calcium channels. Aleksandr Shcheglovitoy, luliia Vitko, Rornan M. Lazarenko, Peihan Orestes, Slobodan M. Todorovic, and Edward Perez-Reyes Cover picture: Adenoviral expression of mitochondria-targeted inorganic polyphosphate (polyP)-hydrolyzing exopolyphosphatase (PPX) was used to reduce polyP levels (top right image) and to investigate the role of polyP for mitochondrial permeability transition pore regulation in cardiac myocytes. DAPI staining revealed mitochondrial polyP localization (bottom right image), polyP-dependent fluorescence (bottom left), and a significant reduction in polyP levels in exopolyphosphatase- expressing cells (bottom right). GFP expression served as a control to monitor the structural effects of PPX expression (see article by Seidimayer et al., 321-331). General Physiology is the study of biological mechanisms emu analytical investigations, which decipher the molecular and cellular mechanisms underlying biological function at all levels of organization. The mission of the Journal of General Physiology is to publish articles that elucidate important biological, chemical, or physical mechanisms of The Journal of General Physiology broad physiological significance. Vol 139 © No 6 # June 2012 Perspectives on: SGP Symposium on Mitochondrial Physiology and Medicine 391 Mitochondria take center stage. Shey-Shing Sheu, Robert T. Dirksen, and Edward N. Pugh Jr. 395 Mitochondrial proteome design: From molecular identity to pathophysiological regulation. Jun Zhang, Amanda Lin, Jared Powers, Maggie P. Lam, Christopher Lotz, David Liem, Edward Lau, Ding Wang, Ning Deng, Paavo Korge, Nobel C. Zong, Hua Cai, James Weiss, and Peipei Ping 407 Metabolic homeostasis of the heart. Robert S. Balaban 415 The renaissance of mitochondrial pH. Jaime Santo-Domingo and Nicolas Demaurex 425 Mitochondrial superoxide flashes: From discovery to new controversies. Lan Wei and Robert T. Dirksen 435 Molecular identities of mitochondrial Ca** influx mechanism: Updated passwords for accessing mitochondrial Ca**-linked health and disease. Jin O-Uchi, Shi Pan, and Shey-Shing Sheu 445 The Pathophysiology of LETM1. Karin Nowikovsky, Tullio Pozzan, Rosario Rizzuto, Luca Scorrano, and Paolo Bernardi 455 What comes first, misshape or dysfunction? The view from metabolic excess. Chad A. Galloway and Yisang Yoon Articles 465 Dynamics of matrix-free Ca** in cardiac mitochondria: two components of Ca** uptake and role of phosphate buffering. An-Chi Wei, Ting Liu, Raimond L. Winslow, and Brian O'Rourke 479 Glutathione/thioredoxin systems modulate mitochondrial H2O2 emission: An experimental-computational study. Miguel Antonio Aon, Brian Alan Stanley, Vidhya Sivakumaran, Jackelyn Melissa Kembro, Brian O'Rourke, Nazareno Paolocci, and Sonia Cortassa Low aqueous solubility of 11-cis-retinal limits the rate of pigment formation and dark adaptation in salamander rods. Rikard Frederiksen, Nicholas P. Boyer, Benjamin Nickle, Kalyan S. Chakrabarti, Yiannis Koutalos, Rosalie K. Crouch, Daniel Oprian, and M. Carter Cornwall Communication 507 Local anesthetic inhibition of a bacterial sodium channel. Sora Lee, Samuel J. Goodchild, and Christopher A. Ahern Cover picture: Schematic of calcium influx and efflux mechanisms in mitochondria, summarizing recent reports on mitochondrial Ca** channels/transporters including the molecular identity of MCU protein. Channels/transporters with unknown molecular identities are shown in black (see Perspective by O-Uchi et al., 435-443).