scholarly journals Brivaracetam Differentially Affects Voltage‐Gated Sodium Currents Without Impairing Sustained Repetitive Firing in Neurons

2014 ◽  
Vol 21 (3) ◽  
pp. 241-251 ◽  
Author(s):  
Isabelle Niespodziany ◽  
Véronique Marie André ◽  
Nathalie Leclère ◽  
Etienne Hanon ◽  
Philippe Ghisdal ◽  
...  
Keyword(s):  
Repetitive Firing ◽  
Sodium Currents ◽  
Voltage Gated

Localization of Amiloride-Sensitive Sodium Current and Voltage-Gated Calcium Currents in Rat Fungiform Taste Cells

2007 ◽  
Vol 98 (4) ◽  
pp. 2483-2487 ◽  
Author(s):  
Albertino Bigiani ◽  
Valeria Cuoghi
Keyword(s):  
Low Voltage ◽  
Calcium Influx ◽  
Sodium Current ◽  
Calcium Currents ◽  
Nerve Endings ◽  
Repetitive Firing ◽  
High Threshold ◽  
Sodium Currents ◽  
Voltage Gated ◽  
Taste Cells

Recent studies have shown that taste cells transducing bitter, sweet, and umami stimuli do not possess high-threshold voltage-gated calcium channels required for synaptic transmission at conventional synapses, suggesting some sort of signal processing inside taste buds prior to the activation of nerve endings. To evaluate whether this is a general paradigm for the physiology of taste reception, we studied the transduction pathway underlying the detection of sodium ions (salty stimulus). In laboratory rodents, Na+ is thought to be transduced, at least in part, through amiloride-sensitive sodium channels (ASSCs). Therefore we used the patch-clamp techniques to analyze the occurrence pattern of amiloride-sensitive sodium currents and voltage-gated calcium currents (both low-voltage-activated T-type current and high-voltage-activated L-type current) among taste cells in rat fungiform papillae. Because taste cells turnover, we focused our attention on cells possessing large voltage-gated sodium currents, a sign of “mature” cells. We found that cells expressing functional ASSCs either did not possess any calcium currents or exhibited only T-type calcium currents, which is believed to play a role in repetitive firing. On the contrary, cells lacking functional ASSCs were endowed with L-type calcium currents, which are thought to mediate calcium influx required for neurotransmitter exocytosis. Therefore our data suggest that sodium-detecting cells are unlikely to use conventional synaptic communication to transfer taste information to nerve endings. Our findings on sodium taste detection support the recent model of taste transduction, involving separate groups of taste cells: chemosensitive cells and cells forming conventional synapses.

scholarly journals Molecular determinants of afferent sensitization in a rat model of cystitis with urothelial barrier dysfunction

2019 ◽  
Vol 122 (3) ◽  
pp. 1136-1146 ◽  
Author(s):  
Nicolas Montalbetti ◽  
James G. Rooney ◽  
Anna C. Rued ◽  
Marcelo D. Carattino
Keyword(s):  
Interstitial Cystitis ◽  
Sensory Neurons ◽  
Rat Model ◽  
Pain Syndrome ◽  
Bladder Pain Syndrome ◽  
Repetitive Firing ◽  
Delayed Rectifier ◽  
Mrna Levels ◽  
Bladder Pain ◽  
Voltage Gated

The internal surface of the urinary bladder is covered by the urothelium, a stratified epithelium that forms an impermeable barrier to urinary solutes. Increased urothelial permeability is thought to contribute to symptom generation in several forms of cystitis by sensitizing bladder afferents. In this report we investigate the physiological mechanisms that mediate bladder afferent hyperexcitability in a rat model of cystitis induced by overexpression in the urothelium of claudin-2 (Cldn2), a tight junction-associated protein upregulated in bladder biopsies from patients with interstitial cystitis/bladder pain syndrome. Patch-clamp studies showed that overexpression of Cldn2 in the urothelium sensitizes a population of isolectin GS-IB4-negative [IB4(−)] bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials. Gene expression analysis revealed a significant increase in mRNA levels of the delayed-rectifier voltage-gated K+ channel (Kv)2.2 and the accessory subunit Kv9.1 in this population of bladder sensory neurons. Consistent with this finding, Kv2/Kv9.1 channel activity was greater in IB4(−) bladder sensory neurons from rats overexpressing Cldn2 in the urothelium than in control counterparts. Likewise, current density of TTX-S voltage-gated Na+ (Nav) channels was greater in sensitized neurons than in control counterparts. Significantly, guangxitoxin-1E (GxTX-1E), a selective blocker of Kv2 channels, blunted the repetitive firing of sensitized IB4(−) sensory neurons. In summary, our studies indicate that an increase in the activity of TTX-S Nav and Kv2/Kv9.1 channels mediates repetitive firing of sensitized bladder sensory neurons in rats with increased urothelial permeability. NEW & NOTEWORTHY Hyperexcitability of sensitized bladder sensory neurons in a rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) results from increased activity of tetrodotoxin-sensitive voltage-gated Na+ and delayed-rectifier voltage-gated K+ (Kv)2/Kv9.1 channels. Of major significance, our studies indicate that Kv2/Kv9.1 channels play a major role in symptom generation in this model of IC/BPS by maintaining the sustained firing of the sensitized bladder sensory neurons.

scholarly journals Focused ultrasound activates voltage-gated calcium channels through depolarizing TRPC1 sodium currents in kidney and skeletal muscle

Theranostics ◽  
2019 ◽  
Vol 9 (19) ◽  
pp. 5517-5531 ◽  
Author(s):  
Scott R. Burks ◽  
Rebecca M. Lorsung ◽  
Matthew E. Nagle ◽  
Tsang-Wei Tu ◽  
Joseph A. Frank
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Focused Ultrasound ◽  
Sodium Currents ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

Benzonatate inhibition of voltage-gated sodium currents

2016 ◽  
Vol 101 ◽  
pp. 179-187 ◽  
Author(s):  
M. Steven Evans ◽  
G. Benton Maglinger ◽  
Anita M. Fletcher ◽  
Stephen R. Johnson
Keyword(s):  
Sodium Currents ◽  
Voltage Gated

Topiramate attenuates voltage-gated sodium currents in rat cerebellar granule cells

1997 ◽  
Vol 231 (3) ◽  
pp. 123-126 ◽  
Author(s):  
Cristina Zona ◽  
Maria Teresa Ciotti ◽  
Massimo Avoli
Keyword(s):  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Sodium Currents ◽  
Cerebellar Granule ◽  
Voltage Gated

scholarly journals Knock-in model of Dravet syndrome reveals a constitutive and conditional reduction in sodium current

2014 ◽  
Vol 112 (4) ◽  
pp. 903-912 ◽  
Author(s):  
Ryan J. Schutte ◽  
Soleil S. Schutte ◽  
Jacqueline Algara ◽  
Eden V. Barragan ◽  
Jeff Gilligan ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Sodium Current ◽  
Dravet Syndrome ◽  
Repetitive Firing ◽  
Gabaergic Interneurons ◽  
Sodium Currents ◽  
Channel Gene ◽  
Sodium Channel Gene ◽  
Current Activity ◽  
Scn1a Mutation

Hundreds of mutations in the SCN1A sodium channel gene confer a wide spectrum of epileptic disorders, requiring efficient model systems to study cellular mechanisms and identify potential therapeutic targets. We recently demonstrated that Drosophila knock-in flies carrying the K1270T SCN1A mutation known to cause a form of genetic epilepsy with febrile seizures plus (GEFS+) exhibit a heat-induced increase in sodium current activity and seizure phenotype. To determine whether different SCN1A mutations cause distinct phenotypes in Drosophila as they do in humans, this study focuses on a knock-in line carrying a mutation that causes a more severe seizure disorder termed Dravet syndrome (DS). Introduction of the DS SCN1A mutation (S1231R) into the Drosophila sodium channel gene para results in flies that exhibit spontaneous and heat-induced seizures with distinct characteristics and lower onset temperature than the GEFS+ flies. Electrophysiological studies of GABAergic interneurons in the brains of adult DS flies reveal, for the first time in an in vivo model system, that a missense DS mutation causes a constitutive and conditional reduction in sodium current activity and repetitive firing. In addition, feeding with the serotonin precursor 5-HTP suppresses heat-induced seizures in DS but not GEFS+ flies. The distinct alterations of sodium currents in DS and GEFS+ GABAergic interneurons demonstrate that both loss- and gain-of-function alterations in sodium currents are capable of causing reduced repetitive firing and seizure phenotypes. The mutation-specific effects of 5-HTP on heat-induced seizures suggest the serotonin pathway as a potential therapeutic target for DS.

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