ON THE COVER
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.
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Probing insulin secretion with a new tool
JGP study explains how chromomycin A2 affects insulin secretion.
Influences: Russian training
Sobolevsky reflects on his unique scientific upbringing in Russia.
Oddballs in the Shaker family: Kv2-related regulatory subunits
Kobertz comments on the family of “silent” Kv2-related regulatory subunits and a new study investigating their assembly idiosyncrasies.
The structure of Orco and its impact on our understanding of olfaction
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
Electrical coupling and its channels
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.
Visualization of expanding fusion pores in secretory cells
Abbineni et al. examine recent imaging work on fusion pores and discuss the dynamics of PI-4,5-P2 accumulation on granule membranes.
Second messenger molecules have a limited spread in olfactory cilia
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.
TREK-1 channels regulate pressure sensitivity and calcium signaling in trabecular meshwork cells
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.
Splicing of an automodulatory domain in Cav1.4 Ca2+ channels confers distinct regulation by calmodulin
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.
A bilobal model of Ca2+-dependent inactivation to probe the physiology of L-type Ca2+ channels
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.
The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry
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.
Pore- and voltage sensor–targeted KCNQ openers have distinct state-dependent actions
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.
Different agonists induce distinct single-channel conductance states in TRPV1 channels
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.
Chromomycin A2 potently inhibits glucose-stimulated insulin secretion from pancreatic β cells
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.
The weak voltage dependence of pannexin 1 channels can be tuned by N-terminal modifications
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.
Ion channels can be allosterically regulated by membrane domains near a de-mixing critical point
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.