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Medical Neurobiology Commons

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Full-Text Articles in Medical Neurobiology

Charge Screening By Internal Ph And Polyvalent Cations As A Mechanism For Activation, Inhibition, And Rundown Of Trpm7/Mic Channels, J. Ashot Kozak, Masayuki Matsushita, Angus C. Nairn, Michael D. Cahalan Nov 2005

Charge Screening By Internal Ph And Polyvalent Cations As A Mechanism For Activation, Inhibition, And Rundown Of Trpm7/Mic Channels, J. Ashot Kozak, Masayuki Matsushita, Angus C. Nairn, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

The Mg2+-inhibited cation (MIC) current, believed to represent activity of TRPM7 channels, is found in lymphocytes and mast cells, cardiac and smooth muscle, and several other eukaryotic cell types. MIC current is activated during whole-cell dialysis with divalent-free internal solutions. Millimolar concentrations of intracellular Mg2+ (or other divalent metal cations) inhibit the channels in a voltage-independent manner. The nature of divalent inhibition and the mechanism of channel activation in an intact cell remain unknown. We show that the polyamines (spermine, spermidine, and putrescine) inhibit the MIC current, also in a voltage-independent manner, with a potency that parallels …


Resting Potential–Dependent Regulation Of The Voltage Sensitivity Of Sodium Channel Gating In Rat Skeletal Muscle In Vivo, Gregory N. Filatov, Martin J. Pinter, Mark M. Rich Aug 2005

Resting Potential–Dependent Regulation Of The Voltage Sensitivity Of Sodium Channel Gating In Rat Skeletal Muscle In Vivo, Gregory N. Filatov, Martin J. Pinter, Mark M. Rich

Neuroscience, Cell Biology & Physiology Faculty Publications

Normal muscle has a resting potential of −85 mV, but in a number of situations there is depolarization of the resting potential that alters excitability. To better understand the effect of resting potential on muscle excitability we attempted to accurately simulate excitability at both normal and depolarized resting potentials. To accurately simulate excitability we found that it was necessary to include a resting potential–dependent shift in the voltage dependence of sodium channel activation and fast inactivation. We recorded sodium currents from muscle fibers in vivo and found that prolonged changes in holding potential cause shifts in the voltage dependence of …


A Developmental Switch In The Response Of Drg Neurons To Ets Transcription Factor Signaling, Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber May 2005

A Developmental Switch In The Response Of Drg Neurons To Ets Transcription Factor Signaling, Simon Hippenmeyer, Eline Vrieseling, Markus Sigrist, Thomas Portmann, Celia Laengle, David R. Ladle, Silvia Arber

Neuroscience, Cell Biology & Physiology Faculty Publications

Two ETS transcription factors of the Pea3 subfamily are induced in subpopulations of dorsal root ganglion (DRG) sensory and spinal motor neurons by target-derived factors. Their expression controls late aspects of neuronal differentiation such as target invasion and branching. Here, we show that the late onset of ETS gene expression is an essential requirement for normal sensory neuron differentiation. We provide genetic evidence in the mouse that precocious ETS expression in DRG sensory neurons perturbs axonal projections, the acquisition of terminal differentiation markers, and their dependence on neurotrophic support. Together, our findings indicate that DRG sensory neurons exhibit a temporal …


Stim1, An Essential And Conserved Component Of Store-Operated Ca2+ Channel Function, Jack Roos, Paul J. Digregorio, Andriy V. Yeromin, Kari Ohlsen, Maria I. Lioudyno, Shenyuan L. Zhang, Olga Safrina, J. Ashot Kozak, Steven L. Wagner, Michael D. Cahalan, Gönül Veliçelebi, Kenneth A. Stauderman May 2005

Stim1, An Essential And Conserved Component Of Store-Operated Ca2+ Channel Function, Jack Roos, Paul J. Digregorio, Andriy V. Yeromin, Kari Ohlsen, Maria I. Lioudyno, Shenyuan L. Zhang, Olga Safrina, J. Ashot Kozak, Steven L. Wagner, Michael D. Cahalan, Gönül Veliçelebi, Kenneth A. Stauderman

Neuroscience, Cell Biology & Physiology Faculty Publications

Store-operated Ca2+ (SOC) channels regulate many cellular processes, but the underlying molecular components are not well defined. Using an RNA interference (RNAi)-based screen to identify genes that alter thapsigargin (TG)-dependent Ca2+ entry, we discovered a required and conserved role of Stim in SOC influx. RNAi-mediated knockdown of Stim in Drosophila S2 cells significantly reduced TG-dependent Ca2+ entry. Patch-clamp recording revealed nearly complete suppression of the Drosophila Ca2+ release-activated Ca2+(CRAC) current that has biophysical characteristics similar to CRAC current in human T cells. Similarly, knockdown of the human homologue STIM1 significantly reduced CRAC channel activity …