Ion Channel Gating

Publication Title: 
Annals of the New York Academy of Sciences

Multiple subsets of nociceptive, parasympathetic, and sympathetic nerves innervate human nasal mucosa. These play carefully coordinated roles in regulating glandular, vascular, and other processes. These functions are vital for cleaning and humidifying ambient air before it is inhaled into the lungs. The recent identification of distinct classes of nociceptive nerves with unique patterns of transient receptor potential sensory receptor ion channel proteins may account for the polymodal, chemo- and mechanicosensitivity of many trigeminal neurons.

Baraniuk, James N.
Merck, Samantha J.
Publication Title: 
Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology

Little is known about the relationship between CF transmembrane conductance regulator (CFTR) gene expression and the corresponding transport of Cl. The phenotypic characteristics of polarized DeltaF508 homozygote CF bronchial epithelial (CFBE41o-) cells were evaluated following transfection with episomal expression vector containing either full-length (6.2kb) wild type (wt) and (4.7kb) DeltaF508CFTR cDNA.

Illek, Beate
Maurisse, Rosalie
Wahler, Logan
Kunzelmann, Karl
Fischer, Horst
Gruenert, Dieter C.
Publication Title: 
Cellular Physiology and Biochemistry: International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology

The flavone apigenin has been previously selected as a potent pharmacological activator of the CFTR Cl(-) channel, however, its utility for the activation of CFTR in vivo is expected to be limited because flavonoids are readily metabolized. We therefore investigated the poorly metabolizable methylether of apigenin, 5,7,4'-trimethoxyflavone (TMF) as a CFTR activator using transepithelial short-circuit current measurements, whole cell and single cell patch clamp techniques, and nasal potential difference (PD) measurements.

Fischer, Horst
Illek, Beate
Publication Title: 
American Journal of Respiratory Cell and Molecular Biology

Therapies to correct the ΔF508 cystic fibrosis transmembrane conductance regulator (CFTR) folding defect require sensitive methods to detect channel activity in vivo. The β₂ adrenergic receptor agonists, which provide the CFTR stimuli commonly used in nasal potential difference assays, may not overcome the channel gating defects seen in ΔF508 CFTR after plasma membrane localization. In this study, we identify an agent, quercetin, that enhances the detection of surface ΔF508 CFTR, and is suitable for nasal perfusion.

Pyle, Louise C.
Fulton, Jennifer C.
Sloane, Peter A.
Backer, Kyle
Mazur, Marina
Prasain, Jeevan
Barnes, Stephen
Clancy, J. P.
Rowe, Steven M.
Publication Title: 
Journal of Molecular and Cellular Cardiology

HIV protease inhibitors (HIV PI) reduce morbidity and mortality of HIV infection but cause multiple untoward effects. Because certain HIV PI evoke production of reactive oxygen species (ROS) and volume-sensitive Cl(-) current (I(Cl,swell)) is activated by ROS, we tested whether HIV PI stimulate I(Cl,swell) in ventricular myocytes. Ritonavir and lopinavir elicited outwardly rectifying Cl(-) currents under isosmotic conditions that were abolished by the selective I(Cl,swell)-blocker DCPIB.

Deng, Wu
Baki, Lia
Yin, Jun
Zhou, Huiping
Baumgarten, Clive M.
Publication Title: 
Molecular Pain

BACKGROUND: Diabetic neuropathy is a common neuropathy associated with paresthaesia and pain. The mechanisms underlying the painful conditions are not well understood. The aim of this study is to investigate the participation of purinergic P2X3 receptors in painful diabetic neuropathy. RESULTS: Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). We showed that mechanical allodynia was induced two weeks after a STZ injection and lasted for at least another seven weeks.

Xu, Guang-Yin
Li, Guangwen
Liu, Ningang
Huang, Li-Yen Mae
Publication Title: 
Beijing Da Xue Xue Bao. Yi Xue Ban = Journal of Peking University. Health Sciences

Short circuit current (I(sc)) technique has been applied in the studies of transepithelial ion transport in various epithelia. Recently it has also been used in the modernization researches on traditional Chinese medicines. This review gives an overview of the basic principle of the I(sc) technique, the targets of measurement, ion transport, ion channel, the general ways of I(sc) research design, the application of I(sc) technology in the researches on traditional Chinese medicines.

Yuan, Jin-song
Li, Kang
Yang, Da-jian
Sui, Li-ying
Liu, Yan
Zhang, Chao
Guo, Chang-jie
Publication Title: 
Nature Neuroscience

A major unresolved issue in treating pain is the paradoxical hyperalgesia produced by the gold-standard analgesic morphine and other opiates. We found that hyperalgesia-inducing treatment with morphine resulted in downregulation of the K(+)-Cl(-) co-transporter KCC2, impairing Cl(-) homeostasis in rat spinal lamina l neurons. Restoring the anion equilibrium potential reversed the morphine-induced hyperalgesia without affecting tolerance. The hyperalgesia was also reversed by ablating spinal microglia.

Ferrini, Francesco
Trang, Tuan
Mattioli, Theresa-Alexandra M.
Laffray, Sophie
Del'Guidice, Thomas
Lorenzo, Louis-Etienne
Castonguay, Annie
Doyon, Nicolas
Zhang, Wenbo
Godin, Antoine G.
Mohr, Daniela
Beggs, Simon
Vandal, Karen
Beaulieu, Jean-Martin
Cahill, Catherine M.
Salter, Michael W.
De Koninck, Yves
Publication Title: 
European biophysics journal: EBJ

A stretch-activated (SA) Cl(-) channel in the plasma membrane of the human mast cell line HMC-1 was identified in outside-out patch-clamp experiments. SA currents, induced by pressure applied to the pipette, exhibited voltage dependence with strong outward rectification (55.1 pS at +100 mV and an about tenfold lower conductance at -100 mV). The probability of the SA channel being open (P (o)) also showed steep outward rectification and pressure dependence.

Wang, Lina
Ding, Guanghong
Gu, Quanbao
Schwarz, Wolfgang
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