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As JGP approaches its centenary, we consider how physiology has changed over the last 100 years and reflect on the journal's role in the physiology community..

Research News

JGP study explores diurnal changes in calcium sources governing BK activity in the SCN.


Aldrich recounts the unique influence that the Yale Physiology Department had on his early career.


Fleming examines a new methodology for measuring the free energy of dimerization in lipid bilayers.

Murrell-Lagnado provides insight into new research revealing the physiological role of lysosomal P2X4 channels.

Milestone in Physiology

Franzini-Armstrong reviews the development of the excitation–contraction coupling field over time.

Hilgemann et al. explain how lipid signaling to membrane proteins involves a hierarchy of mechanisms from lipid binding to membrane domain coalescence.


James and Zagotta discuss how recent cryoEM structures inform our understanding of cyclic nucleotide–binding domain channels.


The molecular mechanisms underlying the inhibition of the cardiac Na+–Ca2+ exchanger by cytoplasmic protons are poorly defined. Using mutagenesis and electrophysiology, John et al. reveal specific residues within this plasma membrane transporter that are important for pH regulation.

Large conductance K+ (BK) channels require intracellular Ca2+ provided by Ca2+ channels to open at physiological membrane potentials. Whitt et al. identify the Ca2+ channel subtypes that activate BK current in the suprachiasmatic nucleus to enable time of day to be encoded by the circadian clock.

P2X4 receptor activation facilitates secretion of pulmonary surfactant from secretory vesicles called lamellar bodies in alveolar epithelial cells. Fois et al. reveal that P2X4 receptors on the lamellar body membranes are activated by ATP stored within the vesicles themselves upon vesicle exocytosis.

Type 1 RyRs (RyR1s) of the sarcoplasmic reticulum signal bidirectionally with plasma membrane dihydropyridine receptors in skeletal muscle. Polster et al. show that isolated cytoplasmic domains of RyR1 can oligomerize, localize to membrane junctions, and restore retrograde signaling.

Voltage-dependent gating in ion channels is achieved by the movement of voltage-sensing arginine residues across an electric field. Carvalho-de-Souza and Bezanilla reveal that the size and hydrophobicity of two non–voltage-sensing residues (L358 and L361) affect voltage dependence in Shaker K+ channels.

New mathematical tools are needed to incorporate existing knowledge into kinetic models of ion channels and other proteins. Salari et al. describe an algebraic transformation that can enforce linearly interdependent parameters into kinetic models in order to test new hypotheses.

In their preceding paper, Salari et al. describe a formalism that allows existing knowledge to be enforced into kinetic models. Here, Navarro et al. present a penalty-based optimization mechanism to incorporate arbitrary parameter relationships and constraints that quantify the behavior of the model.


Quantification of protein dimerization energies in lipid bilayers is hard to achieve, largely due to methodological challenges. Chadda et al. present an expansion of the single-molecule subunit-capture approach that incorporates empirical benchmarks for monomers and dimers, simplifying the process.


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