Issues

JGP study shows that pro-secretory agonists prompt CFTR to assemble into large lipid platforms.

Baylor recollects the time he spent with his mentor, Alan Hodgkin, working on phototransduction in turtle retinas.

Wei-LaPierre and Dirksen discuss new work investigating the molecular events underlying mitoflash biogenesis.

McManus, Werley, and Dempsey highlight new work showing that nicotine rapidly equilibrates in the ER after extracellular application.

Mundiña-Weilenmann and Mattiazzi examine new work revealing the mechanism by which nitroxide modifies uptake of Ca²⁺ into the SR.

Bazmi and Escobar highlight a recent investigation of the mechanisms that regulate Ca²⁺ influx during sympathetic stimulation.

Individual mitochondria undergo an intermittent, all-or-none electrochemical excitation termed “mitoflash.” Feng et al. show that mitoflash occurs following build-up of mitochondrial electrochemical potential and may serve to autoregulate mitochondrial proton electrochemical potential.

Nicotine permeates into the endoplasmic reticulum (ER) where it begins an “inside-out” pathway that leads to addiction. Shivange et al. develop genetically encoded nicotine biosensors and show that nicotine and varenicline equilibrate in the ER within seconds of extracellular application.

Treatment with nitroxyl (HNO) improves cardiac function in failing hearts by inducing release of SR Ca²⁺-ATPase from phospholamban (PLN), thereby enhancing Ca²⁺ reuptake. Keceli et al. use ¹⁵N-edited NMR spectroscopy to show that HNO achieves this by reversibly modifying PLN cysteines 41 and 46.

Intact heart physiology assessed by local-field optical techniques helps decipher cardiac function at the organ level. Here, we found that the phase 1 repolarization rate of the mouse ventricular action potential defines contractility by regulating the deactivation of an L-type Ca²⁺ current.

During a cardiac action potential, the activity of L-type Ca²⁺ channels (LTCCs) is modulated by voltage- and calcium-dependent inactivation processes. Morales et al. show that, in the context of β-adrenergic stimulation, calcium-dependent inactivation directs the regulation of LTCC activity, limiting calcium influx during the action potential.

Subunit concatenation is a powerful technique used to control the assembly of structurally diverse heteromeric receptors such as GABA_ARs. Liao et al. find that existing GABA_AR concatemers do not assemble as expected and describe refinements that allow expression of uniform receptor populations.

The human purinergic receptor P2X4 is an ATP-gated nonselective cation channel expressed in a variety of cells, including hepatocytes and cholangiocytes. Ilyaskin et al. find that the bile acids inhibit P2X4 by stabilizing the channel's closed state, likely by interacting with its transmembrane domain.

Little is known about how CFTR, the Cl⁻ channel that is mutated in cystic fibrosis, interacts with lipids. Abu-Arish et al. show that agents that stimulate salt and fluid secretion reduce CFTR lateral mobility and promote its clustering into ceramide-rich platforms, thereby increasing its surface expression.

Ca²⁺ flux into axon terminals via Ca_V2.1 is the trigger for neurotransmitter release at neuromuscular junctions and many central synapses. Our data raise the possibility that an arginine to proline substitution at residue 1,673 causes a severe neurodevelopmental disorder by making Ca_V2.1 less sensitive to changes in membrane potential.

Muscle fiber contraction involves chemical reactions and structural changes that are sensitive to temperature. Ishii et al. show that rapid heating causes cardiac thin filament sliding, and the data could indicate that thin filaments are partially activated during diastole at mammalian body temperature.