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    Ion channels and other integral plasma membrane proteins interact with a highly heterogeneous two-dimensional solvent hypothesized to be near a de-mixing critical point. Kimchi et al. consider a lattice channel that interacts with solvent heterogeneity through its boundary interactions. Here, the lattice channel (blue sphere) prefers more ordered lipids (blue components), localizing it to a fluctuating blue domain. Near a universal de-mixing transition in the membrane, such a lattice channel’s average activity becomes highly sensitive to perturbations, and the channel’s kinetics acquire a range of timescales from fluctuations of membrane composition. See page 1769.

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ISSN 0022-1295
EISSN 1540-7748

Research News

JGP study explains how chromomycin A2 affects insulin secretion.

Essay

JGP 100th Anniversary

Sobolevsky reflects on his unique scientific upbringing in Russia.

Commentary

Kobertz comments on the family of “silent” Kv2-related regulatory subunits and a new study investigating their assembly idiosyncrasies.

Zufall and Domingos discuss the significance of the recent structure of the insect odorant co-receptor Orco to the field of olfaction.

Milestone in Physiology

JGP 100th Anniversary

Harris explores the development of our current understanding of electrical coupling between cells and the channels that mediate it, highlighting the contributions of the Journal of General Physiology.

Viewpoint

Abbineni et al. examine recent imaging work on fusion pores and discuss the dynamics of PI-4,5-P2 accumulation on granule membranes.

Article

Olfactory responses in the cilia of olfactory receptor cells last for longer than 10 s, which cannot be explained by free diffusion of second messengers. Takeuchi and Kurahashi show that these signaling molecules have a limited spread and remain at the site of generation for a long time.

The trabecular meshwork (TM) plays a fundamental role in intraocular pressure regulation, but its mechanotransduction pathway is poorly understood. Yarishkin et al. show that the mechanosensing channel TREK-1 regulates TM membrane potential, pressure sensitivity, calcium homeostasis, and impedance.

Cav1.4 Ca2+ channels provide maintained Ca2+ entry to support sustained neurotransmitter release, but a retinal splice variant exhibits calmodulin-dependent inactivation. Williams et al. show that the N lobe of calmodulin is involved in this process as well as Ca2+-dependent enhancement of channel activation.

L-type calcium channels undergo Ca2+-dependent inactivation (CDI) in order to precisely control the entry of Ca2+ into cells such as cardiomyocytes. Limpitikul et al. develop a bilobal model of CDI and use it to understand the pathogenesis of arrhythmias associated with mutations in CaM.

Atypical substitutions in the S6 activation gate sequence distinguish “regulatory” Kv subunits, which cannot homotetramerize due to T1 self-incompatibility. Pisupati et al. show that such substitutions in Kv6 work together with self-incompatibility to restrict Kv2:Kv6 heteromeric stoichiometry to 3:1.

The KCNQ2-5 voltage-gated potassium channels are activated by a number of different compounds that shift the voltage dependence of activation to more negative voltages. Wang et al. show that pore- and voltage sensor–targeted activators have different state-dependent actions and therefore distinct mechanisms.

TRPV1 is a polymodal ion channel that can be activated by lysophosphatidic acid (LPA), resulting in pain. Here we show that TRPV1 activation by LPA promotes a distinct open state with a different single-channel conductance from that induced by capsaicin.

Communication

Drugs that target insulin secretion are useful to understand β cell function and the pathogenesis of diabetes. Kalwat et al. investigate an aureolic acid that inhibits insulin secretion and reveal that it disrupts Wnt signaling, interferes with gene expression, and suppresses Ca2+ influx in β cells.

Voltage stimulation is commonly used to study pannexin 1 (Panx1). However, whether Panx1 is a voltage-gated channel remains controversial. Michalski et al. demonstrate that Panx1 is a channel with weak voltage dependence, whose activity can be tuned by N-terminal modifications.

Hypothesis

The plasma membrane is close to an Ising critical point, below which it would separate into two phases. Kimchi et al. explore the consequences for ion channel function using a lattice Ising model and find that channel kinetics can be influenced by the proximity of the membrane to a critical point.

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