The Experts below are selected from a list of 204 Experts worldwide ranked by ideXlab platform
X Shawn Z Xu - One of the best experts on this subject based on the ideXlab platform.
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c elegans trp family protein trp 4 is a pore forming subunit of a native mechanotransduction channel
Neuron, 2010Co-Authors: Lijun Kang, William R Schafer, X Shawn Z XuAbstract:Summary Mechanotransduction channels mediate several common sensory modalities such as hearing, touch, and proprioception; however, very little is known about the molecular identities of these channels. Many TRP family channels have been implicated in mechanosensation, but none have been demonstrated to form a mechanotransduction channel, raising the question of whether TRP proteins simply play indirect roles in mechanosensation. Using Caenorhabditis elegans as a model, here we have recorded a mechanosensitive conductance in a ciliated mechanosensory neuron in vivo. This conductance develops very rapidly upon mechanical stimulation with its latency and Activation Time Constant reaching the range of microseconds, consistent with mechanical gating of the conductance. TRP-4, a TRPN (NOMPC) subfamily channel, is required for this conductance. Importantly, point mutations in the predicted pore region of TRP-4 alter the ion selectivity of the conductance. These results indicate that TRP-4 functions as an essential pore-forming subunit of a native mechanotransduction channel.
Lijun Kang - One of the best experts on this subject based on the ideXlab platform.
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c elegans trp family protein trp 4 is a pore forming subunit of a native mechanotransduction channel
Neuron, 2010Co-Authors: Lijun Kang, William R Schafer, X Shawn Z XuAbstract:Summary Mechanotransduction channels mediate several common sensory modalities such as hearing, touch, and proprioception; however, very little is known about the molecular identities of these channels. Many TRP family channels have been implicated in mechanosensation, but none have been demonstrated to form a mechanotransduction channel, raising the question of whether TRP proteins simply play indirect roles in mechanosensation. Using Caenorhabditis elegans as a model, here we have recorded a mechanosensitive conductance in a ciliated mechanosensory neuron in vivo. This conductance develops very rapidly upon mechanical stimulation with its latency and Activation Time Constant reaching the range of microseconds, consistent with mechanical gating of the conductance. TRP-4, a TRPN (NOMPC) subfamily channel, is required for this conductance. Importantly, point mutations in the predicted pore region of TRP-4 alter the ion selectivity of the conductance. These results indicate that TRP-4 functions as an essential pore-forming subunit of a native mechanotransduction channel.
G. Gueret - One of the best experts on this subject based on the ideXlab platform.
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Sodium Channel Na_V1.5 Expression is Enhanced in Cultured Adult Rat Skeletal Muscle Fibers
Journal of Membrane Biology, 2010Co-Authors: J. Morel, F. Rannou, H. Talarmin, M. A. Giroux-metges, J. P. Pennec, G. Dorange, G. GueretAbstract:This study analyzes changes in the distribution, electrophysiological properties, and proteic composition of voltage-gated sodium channels (Na_V) in cultured adult rat skeletal muscle fibers. Patch clamp and molecular biology techniques were carried out in flexor digitorum brevis (FDB) adult rat skeletal muscle fibers maintained in vitro after cell dissociation with collagenase. After 4 days of culture, an increase of the Na_V1.5 channel type was observed. This was confirmed by an increase in TTX-resistant channels and by Western blot test. These channels exhibited increased Activation Time Constant (τ_m) and reduced conductance, similar to what has been observed in denervated muscles in vivo, where the density of Na_V1.5 was increasing progressively after denervation. By real-Time polymerase chain reaction, we found that the expression of β subunits was also modified, but only after 7 days of culture: increase in β_1 without β_4 modifications. β_1 subunit is known to induce a negative shift of the inActivation curve, thus reducing current amplitude and duration. At day 7, τ_h was back to normal and τ_m still increased, in agreement with a decrease in sodium current and conductance at day 4 and normalization at day 7. Our model is a useful tool to study the effects of denervation in adult muscle fibers in vitro and the expression of sodium channels. Our data evidenced an increase in Na_V1.5 channels and the involvement of β subunits in the regulation of sodium current and fiber excitability.
Sheng-nan Wu - One of the best experts on this subject based on the ideXlab platform.
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Inhibitory Effective Perturbations of Cilobradine (DK-AH269), A Blocker of HCN Channels, on the Amplitude and Gating of Both Hyperpolarization-Activated Cation and Delayed-Rectifier Potassium Currents
International Journal of Molecular Sciences, 2020Co-Authors: Te-ling Lu, Te Jung Lu, Sheng-nan WuAbstract:Cilobradine (CIL, DK-AH269), an inhibitor of hyperpolarization-activated cation current (Ih), has been observed to possess pro-arrhythmic properties. Whether and how CIL is capable of perturbing different types of membrane ionic currents existing in electrically excitable cells, however, is incompletely understood. In this study, we intended to examine possible modifications by it or other structurally similar compounds of ionic currents in pituitary tumor (GH3) cells and in heart-derived H9c2 cells. The standard whole-cell voltage-clamp technique was performed to examine the effect of CIL on ionic currents. GH3-cell exposure to CIL suppressed the density of hyperpolarization-evoked Ih in a concentration-dependent manner with an effective IC50 of 3.38 μM. Apart from its increase in the Activation Time Constant of Ih during long-lasting hyperpolarization, the presence of CIL (3 μM) distinctly shifted the steady-state Activation curve of Ih triggered by a 2-s conditioning pulse to a hyperpolarizing direction by 10 mV. As the impedance-frequency relation of Ih was studied, its presence raised the impedance magnitude at the resonance frequency induced by chirp voltage. CIL also suppressed delayed-rectifier K+ current (IK(DR)) followed by the accelerated inActivation Time course of this current, with effective IC50 (measured at late IK(DR)) or KD value of 3.54 or 3.77 μM, respectively. As the CIL concentration increased 1 to 3 μM, the inActivation curve of IK(DR) elicited by 1- or 10-s conditioning pulses was shifted to a hyperpolarizing potential by approximately 10 mV, and the recovery of IK(DR) inActivation during its presence was prolonged. The peak Na+ current (INa) during brief depolarization was resistant to being sensitive to the presence of CIL, yet to be either decreased by subsequent addition of A-803467 or enhanced by that of tefluthrin. In cardiac H9c2 cells, unlike the CIL effect, the addition of either ivabradine or zatebradine mildly led to a lowering in IK(DR) amplitude with no conceivable change in the inActivation Time course of the current. Taken together, the compound like CIL, which was tailored to block hyperpolarization-activated cation (HCN) channels effectively, was also capable of altering the amplitude and gating of IK(DR), thereby influencing the functional activities of electrically excitable cells, such as GH3 cells.
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Important modifications by sugammadex, a modified γ-cyclodextrin, of ion currents in differentiated NSC-34 neuronal cells
BMC Neuroscience, 2017Co-Authors: Yi Ching Lo, Yan-ming Huang, Yu-ting Tseng, Sheng-nan WuAbstract:Background Sugammadex (SGX) is a modified γ-cyclodextrin used for reversal of steroidal neuromuscular blocking agents during general anesthesia. Despite its application in clinical use, whether SGX treatment exerts any effects on membrane ion currents in neurons remains largely unclear. In this study, effects of SGX treatment on ion currents, particularly on delayed-rectifier K^+ current [ I _K(DR)], were extensively investigated in differentiated NSC-34 neuronal cells. Results After cells were exposed to SGX (30 μM), there was a reduction in the amplitude of I _K(DR) followed by an apparent slowing in current Activation in response to membrane depolarization. The challenge of cells with SGX produced a depolarized shift by 15 mV in the Activation curve of I _K(DR) accompanied by increased gating charge of this current. However, the inActivation curve of I _K(DR) remained unchanged following SGX treatment, as compared with that in untreated cells. According to a minimal reaction scheme, the lengthening of Activation Time Constant of I _K(DR) caused by cell treatment with different SGX concentrations was quantitatively estimated with a dissociation Constant of 17.5 μM, a value that is clinically achievable. Accumulative slowing in I _K(DR) Activation elicited by repetitive stimuli was enhanced in SGX-treated cells. SGX treatment did not alter the amplitude of voltage-gated Na^+ currents. In SGX-treated cells, dexamethasone (30 μM), a synthetic glucocorticoid, produced little or no effect on L-type Ca^2+ currents, although it effectively suppressed the amplitude of this current in untreated cells. Conclusions The treatment of SGX may influence the amplitude and gating of I _K(DR) and its actions could potentially contribute to functional activities of motor neurons if similar results were found in vivo.
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Characterization of chromanol 293B-induced block of the delayed-rectifier K+ current in heart-derived H9c2 cells.
Life Sciences, 2005Co-Authors: Yi Ching Lo, Su Rong Yang, Mei Han Huang, Sheng-nan WuAbstract:The effects of chromanol 293B on ion currents in rat embryonic heart-derived H9c2 cells were investigated in this study. Chromanol 293B suppressed the amplitude of delayed rectified K+ current (IK) in a concentration-dependent manner. The IC50 value for chromanol 293B-induced inhibition of IK was 8 μM. The IK present in these cells, the electrical properties of which resembled those for the Kv2.1-related K+ current, was sensitive to inhibition by quinidine or dendrotoxin, yet not by pandinotoxin-Kα, E-4031 or apamin. Chromanol 293B reduced the Activation Time Constant of IK and the effective gating charge of this channel. However, little or no modification in the steady-state inActivation of IK in response to long-lasting conditioning pulses could be demonstrated in the presence of chromanol 293B. These results clearly demonstrate that chromanol 293B can effectively interact with the K+ channel functionally expressed in H9c2 myoblasts. The chromanol 293B-induced inhibition of these channels could primarily be attributed to open channel block.
M. B. Sedova - One of the best experts on this subject based on the ideXlab platform.
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Influence of the external concentration of potassium ions on functioning of voltage-dependent potassium channels in GH_3 cells
Neurophysiology, 1995Co-Authors: A. V. Grishchenko, N. M. Berezetskaya, G. E. Weinreb, N. I. Kononenko, M. B. SedovaAbstract:The patch-clamp technique in a whole-cell configuration was used to study the influence of the external concentration of potassium ions on the characteristics of the voltage-dependent potassium current in the plasma membrane of GH_3 cells (a cell line isolated from the rat pituitary body tumor). The [K^+]_ out shift from 5 to 100 mM induced a monotonic increase in potassium current with a Constant difference between the testing potential and potassium equilibrium potential. The dependence of an Activation Time Constant, τ_ n , and a steady-state Activation, n ∞, of the potassium current on [K^+]_ out is of a distinct non-monotononic character with the extremum at 20 mM. Our experiments and theoretical speculations allow us to suppose that the interaction of potassium ions with slowly relaxing charged channel-forming protein groups induced the observed effects.
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Influence of the external concentration of potassium ions on functioning of voltage-dependent potassium channels in GH3 cells
Neurophysiology, 1995Co-Authors: A. V. Grishchenko, N. M. Berezetskaya, G. E. Weinreb, N. I. Kononenko, M. B. SedovaAbstract:The patch-clamp technique in a whole-cell configuration was used to study the influence of the external concentration of potassium ions on the characteristics of the voltage-dependent potassium current in the plasma membrane of GH3 cells (a cell line isolated from the rat pituitary body tumor). The [K+] out shift from 5 to 100 mM induced a monotonic increase in potassium current with a Constant difference between the testing potential and potassium equilibrium potential. The dependence of an Activation Time Constant, τ n , and a steady-state Activation,n∞, of the potassium current on [K+] out is of a distinct non-monotononic character with the extremum at 20 mM. Our experiments and theoretical speculations allow us to suppose that the interaction of potassium ions with slowly relaxing charged channel-forming protein groups induced the observed effects.
