Table Of ContentGeneral 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 cap-
saicin (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 exopolyphos-
phatase (PPX) was used to reduce polyP levels (top right image) and to investigate the role of polyP for mitochondrial per-
meability 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).
