Sodium Currents in Subthalamic Nucleus Neurons From Nav1.6-Null Mice

2004 ◽  
Vol 92 (2) ◽  
pp. 726-733 ◽  
Author(s):  
Michael Tri H. Do ◽  
Bruce P. Bean
Keyword(s):  
Subthalamic Nucleus ◽  
Sodium Channels ◽  
Sodium Current ◽  
Great Majority ◽  
Purkinje Neurons ◽  
Wild Type ◽  
Decay Kinetics ◽  
Persistent Currents ◽  
Resurgent Current ◽  
Resurgent Sodium Current

In some central neurons, including cerebellar Purkinje neurons and subthalamic nucleus (STN) neurons, TTX-sensitive sodium channels show unusual gating behavior whereby some channels open transiently during recovery from inactivation. This “resurgent” sodium current is effectively activated immediately after action potential-like waveforms. Earlier work using Purkinje neurons suggested that the great majority of resurgent current originates from Nav1.6 sodium channels. Here we used a mouse mutant lacking Nav1.6 to explore the contribution of these channels to resurgent, transient, and persistent components of TTX-sensitive sodium current in STN neurons. The resurgent current of STN neurons from Nav1.6−/− mice was reduced by 63% relative to wild-type littermates, a less dramatic reduction than that observed in Purkinje neurons recorded under identical conditions. The transient and persistent currents of Nav1.6−/− STN neurons were reduced by ∼40 and 55%, respectively. The resurgent current present in Nav1.6−/− null STN neurons was similar in voltage dependence to that in wild-type STN and Purkinje neurons, differing only in having somewhat slower decay kinetics. These results show that sodium channels other than Nav1.6 can make resurgent sodium current much like that from Nav1.6 channels.

scholarly journals A distinct pool of Nav1.5 channels at the lateral membrane of murine ventricular cardiomyocytes

2019 ◽  
Author(s):  
Jean-Sébastien Rougier ◽  
Maria C. Essers ◽  
Ludovic Gillet ◽  
Sabrina Guichard ◽  
Stephan Sonntag ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Sodium Channels ◽  
Sodium Current ◽  
Pdz Domain ◽  
Adaptor Protein ◽  
Cardiac Cells ◽  
Binding Motif ◽  
Wild Type ◽  
Lateral Membrane ◽  
T Tubules

AbstractBackgroundIn cardiac ventricular muscle cells, the presence of voltage-gated sodium channels Nav1.5 at the lateral membrane depends in part on the interaction between the dystrophin-syntrophin complex and the Nav1.5 C-terminal PDZ-domain-binding sequence Ser-Ile-Val (SIV motif). α1-Syntrophin, a PDZ-domain adaptor protein, mediates the interaction between Nav1.5 and dystrophin at the lateral membrane of cardiac cells. Using the cell-attached patch-clamp approach on cardiomyocytes expressing Nav1.5 in which the SIV motif is deleted (ΔSIV), sodium current (INa) recordings from the lateral membrane revealed an SIV-motif-independent INa. Since immunostainings have suggested that Nav1.5 is expressed in transverse (T-) tubules, this remaining INa might be conducted by channels in the T-tubules. Of note, a recent study using heterologous expression systems showed that α1-syntrophin also interacts with the Nav1.5 N-terminus, which may explain the SIV-motif independent INa at the lateral membrane of cardiomyocytes.AimTo address the role of α1-syntrophin in regulating the INa at the lateral membrane of cardiac cells.Methods and resultsPatch-clamp experiments in cell-attached configuration were performed on the lateral membranes of wild-type, α1-syntrophin knock-down, and ΔSIV ventricular mouse cardiomyocytes. Compared to wild-type, a reduction of the lateral INa was observed in myocytes from α1-syntrophin knockdown hearts. However, similar to ΔSIV myocytes, a remaining INa was still recorded. In addition, cell-attached INa recordings from lateral membrane did not differ significantly between non-detubulated and detubulated ΔSIV cardiomyocytes. Lastly, we obtained evidence suggesting that cell-attached patch-clamp experiments on the lateral membrane cannot record currents conducted by channels in T-tubules such as calcium channels.ConclusionAltogether, these results suggest the presence of a sub-pool of sodium channels at the lateral membrane of cardiomyocytes that is independent of α1-syntrophin and the PDZ-binding motif of Na 1.5, located in membrane domains outside of T-tubules. The question of a T-tubular pool of Nav1.5 channels however remains open.

scholarly journals FGF14 modulates resurgent sodium current in mouse cerebellar Purkinje neurons

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Haidun Yan ◽  
Juan L Pablo ◽  
Chaojian Wang ◽  
Geoffrey S Pitt
Keyword(s):  
Sodium Current ◽  
Direct Interaction ◽  
Purkinje Neurons ◽  
Repetitive Firing ◽  
Spinocerebellar Ataxias ◽  
Channel Inactivation ◽  
C Terminus ◽  
N Terminus ◽  
Resurgent Current ◽  
Cerebellar Purkinje Neurons

Rapid firing of cerebellar Purkinje neurons is facilitated in part by a voltage-gated Na+ (NaV) ‘resurgent’ current, which allows renewed Na+ influx during membrane repolarization. Resurgent current results from unbinding of a blocking particle that competes with normal channel inactivation. The underlying molecular components contributing to resurgent current have not been fully identified. In this study, we show that the NaV channel auxiliary subunit FGF14 ‘b’ isoform, a locus for inherited spinocerebellar ataxias, controls resurgent current and repetitive firing in Purkinje neurons. FGF14 knockdown biased NaV channels towards the inactivated state by decreasing channel availability, diminishing the ‘late’ NaV current, and accelerating channel inactivation rate, thereby reducing resurgent current and repetitive spiking. Critical for these effects was both the alternatively spliced FGF14b N-terminus and direct interaction between FGF14b and the NaV C-terminus. Together, these data suggest that the FGF14b N-terminus is a potent regulator of resurgent NaV current in cerebellar Purkinje neurons.

scholarly journals Modulation of neuronal sodium channels by the sea anemone peptide BDS-I

2012 ◽  
Vol 107 (11) ◽  
pp. 3155-3167 ◽  
Author(s):  
Pin Liu ◽  
Sooyeon Jo ◽  
Bruce P. Bean
Keyword(s):  
Sodium Channels ◽  
Pyramidal Neurons ◽  
Sodium Current ◽  
Neuroblastoma Cells ◽  
Specific Inhibitor ◽  
Receptor Site ◽  
Sea Anemone ◽  
Purkinje Neurons ◽  
High Potency ◽  
Amino Acid Peptide

Blood-depressing substance I (BDS-I), a 43 amino-acid peptide from sea anemone venom, is used as a specific inhibitor of Kv3-family potassium channels. We found that BDS-I acts with even higher potency to modulate specific types of voltage-dependent sodium channels. In rat dorsal root ganglion (DRG) neurons, 3 μM BDS-I strongly enhanced tetrodotoxin (TTX)-sensitive sodium current but weakly inhibited TTX-resistant sodium current. In rat superior cervical ganglion (SCG) neurons, which express only TTX-sensitive sodium current, BDS-I enhanced current elicited by small depolarizations and slowed decay of currents at all voltages (EC50 ∼ 300 nM). BDS-I acted with exceptionally high potency and efficacy on cloned human Nav1.7 channels, slowing inactivation by 6-fold, with an EC50 of approximately 3 nM. BDS-I also slowed inactivation of sodium currents in N1E-115 neuroblastoma cells (mainly from Nav1.3 channels), with an EC50 ∼ 600 nM. In hippocampal CA3 pyramidal neurons (mouse) and cerebellar Purkinje neurons (mouse and rat), BDS-I had only small effects on current decay (slowing inactivation by 20–50%), suggesting relatively weak sensitivity of Nav1.1 and Nav1.6 channels. The biggest effect of BDS-I in central neurons was to enhance resurgent current in Purkinje neurons, an effect reflected in enhancement of sodium current during the repolarization phase of Purkinje neuron action potentials. Overall, these results show that BDS-I acts to modulate sodium channel gating in a manner similar to previously known neurotoxin receptor site 3 anemone toxins but with different isoform sensitivity. Most notably, BDS-I acts with very high potency on human Nav1.7 channels.

Sodium Currents in Neurons From the Rostroventrolateral Medulla of the Rat

2003 ◽  
Vol 90 (3) ◽  
pp. 1635-1642 ◽  
Author(s):  
Ilya A. Rybak ◽  
Krzysztof Ptak ◽  
Natalia A. Shevtsova ◽  
Donald R. McCrimmon
Keyword(s):  
Sodium Channels ◽  
Sodium Current ◽  
Cell Voltage ◽  
Kinetic Properties ◽  
Persistent Sodium Current ◽  
Sodium Currents ◽  
Bötzinger Complex ◽  
Window Current ◽  
Bursting Activity

Rapidly inactivating and persistent sodium currents have been characterized in acutely dissociated neurons from the area of rostroventrolateral medulla that included the pre-Bötzinger Complex. As demonstrated in many studies in vitro, this area can generate endogenous rhythmic bursting activity. Experiments were performed on neonate and young rats (P1-15). Neurons were investigated using the whole cell voltage-clamp technique. Standard activation and inactivation protocols were used to characterize the steady-state and kinetic properties of the rapidly inactivating sodium current. Slow depolarizing ramp protocols were used to characterize the noninactivating sodium current. The “window” component of the rapidly inactivating sodium current was calculated using mathematical modeling. The persistent sodium current was revealed by subtraction of the window current from the total noninactivating sodium current. Our results provide evidence of the presence of persistent sodium currents in neurons of the rat rostroventrolateral medulla and determine voltage-gated characteristics of activation and inactivation of rapidly inactivating and persistent sodium channels in these neurons.

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