【摘 要】
：
Transient receptor potential melastatin 2 (TRPM2) channel fulfills an important role in oxidative stress signaling in immune and other cells, to which local extracellular acidosis is known to occur un
【机 构】
：
Institute of Membrane and Systems Biology,Faculty of Biological Sciences,University of Leeds,Leeds L
【出 处】
：
The 3rd Ion Channel Conference: Ion channels-Structure, Func
论文部分内容阅读
Transient receptor potential melastatin 2 (TRPM2) channel fulfills an important role in oxidative stress signaling in immune and other cells, to which local extracellular acidosis is known to occur under physiological or pathological conditions and impose significant effects on their functions.Here, we investigated whether the ADP-ribose-activated TRPM2 channel is a target for modulation by extracellular acidic pH by patch clamp recording of HEK293 cells expressing hTRPM2 channel.Induced whole cell or single channel currents were rapidly inhibited upon subsequent exposure to acidic pH.The inhibition in the steady state was complete, voltage-independent, and pH-independent in the range of pH 4.0-6.0.The inhibition was irreversible upon returning to pH 7.3, suggesting channel inactivation.In contrast, exposure of closed channels to acidic pH reduced the subsequent channel activation in a pH-dependent manner with an IC50 for H+ of 20 μM (pH 4.7) and rendered subsequent current inhibition largely reversible, indicating differential or state-dependent inhibition and inactivation.Alanine substitution of residues in the outer vestibule of the pore including Lys952 and Asp1002 significantly slowed down or reduced acidic pH-induced inhibition and prevented inactivation.The results suggest that acidic pH acts as a negative feedback mechanism where protons bind to the outer vestibule of the TRPM2 channel pore and inhibit the TRPM2 channels in a state-dependent manner.
其他文献
Signals of painful diabetic neuropathy (PDN) are believed to originate in the peripheral nervous system.But its peripheral mechanism ofhyperalgesia has remained elusive.Traditionally, the number of pr
Mycobacterium tuberculosis is known to have a very thick and hydrophobic outer membrane, due to richness in long hydrophobic mycolic acids.Nutrition and waste transportation across M.tuberculosis memb
This experiment was performed to investigate whether methanol-extract of Zizyphi Spinosi Semen (MEZSS) has hypnotic effects and/or enhances pentobarbital-induced sleep behaviors through the γ-aminobut
In an attempt to elucidate the molecular basis of vertebrate olfactory signal transduction, we have recently conducted a proteomic screen for cilial membrane proteins of mouse olfactory sensory neuron
As the prototypical Ca2+ sensor, calmodulin (CaM) is widely expressed in all eukaryotic cells, mediating a variety of cellular signaling processes.A diverse array of target proteins has been identifie
Interstitial Cells of Cajal (ICCs) were considered as the pacemaker cells in gastrointestinal(GI) tract.We isolated ICCs from the small intestine of Balb/C mouse and measured the membrane potential an
Vascular endothelial cells respond to blood flow-induced shear stress by generating vaso-relaxing factors such as NO, which prevents abnormal vaso-constrictions and maintains vessels in a relatively d
Objective: To evaluate changes of expression in spinal dorsal horn of rat chronic post-thoracotomy pain (CPTP) model.Methods: 20 adult male Sprague-Dawley rats, weighing 250 ~350g, were randomly divid
Store-operated calcium entry (SOCE) is mediated through the specific plasma membrane channels in response to the depletion of Ca2+ from intracellular Ca2+ stores.TRPC1, STIM1 and Orail may involve in
TRPV4 is a Ca2+-permeable channel and is sensitive to osmotic and mechanical stimuli as well as thermal stimuli.TRPV4 protein expresses widely in various kinds of tissues.In the cardiac myocytes, TRPV