Layer-Specific Properties of the Persistent Sodium Current in Sensorimotor Cortex

2006 ◽  
Vol 95 (6) ◽  
pp. 3460-3468 ◽  
Author(s):  
P. Aracri ◽  
E. Colombo ◽  
M. Mantegazza ◽  
P. Scalmani ◽  
G. Curia ◽  
...  
Keyword(s):  
Sensorimotor Cortex ◽  
Time Course ◽  
Pyramidal Neurons ◽  
Sodium Current ◽  
Peak Amplitude ◽  
Persistent Sodium Current ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation ◽  
Steady State Inactivation ◽  
Layer V

We evaluated the characteristics of the persistent sodium current ( INaP) in pyramidal neurons of layers II/III and V in slices of rat sensorimotor cortex using whole cell patch-clamp recordings. In both layers, INaP began activating around −60 mV and was half-activated at −43 mV. The INaP peak amplitude and density were significantly higher in layer V. The voltage-dependent INaP steady-state inactivation occurred at potentials that were significantly more positive in layer V ( V1/2: −42.3 ± 1.1 mV) than in layer II/III ( V1/2: −46.8 ± 1.6 mV). In both layers, a current fraction corresponding to about 25% of the maximal peak amplitude did not inactivate. The time course of INaP inactivation and recovery from inactivation could be fitted with a biexponential function. In layer V pyramidal neurons the faster time constant of development of inactivation had variable values, ranging from 158.0 to 1,133.8 ms, but it was on average significantly slower than that in layer II/III (425.9 ± 80.5 vs. 145.8 ± 18.2 ms). In both layers, INaP did not completely inactivate even with very long conditioning depolarizations (40 s at −10 mV). Recovery from inactivation was similar in the two layers. Layer V intrinsically bursting and regular spiking nonadapting neurons showed particularly prolonged depolarized plateau potentials when Ca2+ and K+ currents were blocked and slower early phase of INaP development of inactivation. The biexponential kinetics characterizing the time-dependent inactivation of INaP in layers II/III and V indicates a complex inactivating process that is incomplete, allowing a residual “persistent” current fraction that does not inactivate. Moreover, our data indicate that INaP has uneven inactivation properties in pyramidal neurons of different layers of rat sensorimotor cortex. The higher current density, the rightward shifted voltage dependency of inactivation as well the slower kinetics of inactivation characterizing INaP in layer V with respect to layer II/III pyramidal neurons may play a significant role in their ability to fire recurrent action potential bursts, as well in the high susceptibility to generate epileptic events.

Acute effects of repetitive depolarization on sodium current in chick myocytes

1991 ◽  
Vol 260 (6) ◽  
pp. H1810-H1818
Author(s):  
M. R. Gold ◽  
G. R. Strichartz
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Complete Recovery ◽  
Acute Effects ◽  
Na Current ◽  
Patch Clamp Technique ◽  
Membrane Hyperpolarization ◽  
Atrial Cells ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation

Acute effects of repetitive depolarization on the inward Na+ current (INa) of cultured embryonic chick atrial cells were studied using the whole cell patch-clamp technique. Stimulation rates of 1 Hz or greater produced a progressive decrement of peak INa. With depolarizations to 0 mV of 150-ms duration, applied at 2 Hz from a holding potential of -100 mV, the steady-state decrement was approximately 20%. The magnitude of this effect increased with stimulation frequency and with test potential depolarization and decreased with membrane hyperpolarization. Analysis of INa kinetics revealed that reactivation was sufficiently slow to preclude complete recovery from inactivation with interpulse intervals less than 1,000 ms. Moreover, reactivation accelerated markedly with membrane hyperpolarization, in parallel with the response to repetitive stimulation. The multiexponential time course of recovery of peak INa from repetitive depolarization was similar to that observed after single stimuli; however, there was a shift toward a greater proportion of current recovering with the slower of two time constants. It is concluded that incomplete recovery from inactivation is responsible for the decrement in INa observed with short interpulse intervals.

Bupivacaine Inhibition of L-Type Calcium Current in Ventricular Cardiomyocytes of Hamster 

1997 ◽  
Vol 87 (4) ◽  
pp. 926-934 ◽  
Author(s):  
Kenneth L. Rossner ◽  
Kenneth J. Freese
Keyword(s):  
Peak Amplitude ◽  
Ca Channel ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Inactivation Curve ◽  
Whole Cell Patch Clamp ◽  
Recovery From Inactivation ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Time Dependencies

Background The local anesthetic bupivacaine is cardiotoxic when accidentally injected into the circulation. Such cardiotoxicity might involve an inhibition of cardiac L-type Ca2+ current (ICa,L). This study was designed to define the mechanism of bupivacaine inhibition of ICa,L. Methods Cardiomyocytes were enzymatically dispersed from hamster ventricles. Certain voltage- and time-dependencies of ICa,L were recorded using the whole-cell patch clamp method in the presence and absence of different concentrations of bupivacaine. Results Bupivacaine, in a concentration-dependent manner (10-300 microM), tonically inhibited the peak amplitude of ICa,L. The inhibition was characterized by an increase in the time of recovery from inactivation and a negative-voltage shift of the steady-state inactivation curve. The inhibition was shown to be voltage-dependent, and the peak amplitude of ICa,L could not be restored to control levels by a wash from bupivacaine. Conclusions The inhibition of ICa,L appears, in part, to result from bupivacaine predisposing L-type Ca channels to the inactivated state. Data from washout suggest that there may be two mechanisms of inhibition at work. Bupivacaine may bind with low affinity to the Ca channel and also affect an unidentified metabolic component that modulates Ca channel function.

scholarly journals Variation in sodium current amplitude between vasopressin and oxytocin hypothalamic supraoptic neurons

2013 ◽  
Vol 109 (4) ◽  
pp. 1017-1024 ◽  
Author(s):  
Reese Scroggs ◽  
Lie Wang ◽  
Ryoichi Teruyama ◽  
William E. Armstrong
Keyword(s):  
Time Course ◽  
Sodium Current ◽  
Recovery From Inactivation ◽  
Double Exponential ◽  
Significant Difference ◽  
Steady State Inactivation ◽  
Neuronal Types ◽  
Rate Of Recovery ◽  
Firing Properties ◽  
Supraoptic Neurons

Biophysical characteristics of tetrodotoxin-sensitive sodium (Na+) currents were studied in vasopressin (VP) and oxytocin (OT) supraoptic neurons acutely isolated from rat hypothalamus. Na+ current density (pA/pF) was significantly greater in VP neurons than in OT neurons. No significant difference between VP and OT neurons was detected regarding the voltage dependence of activation and steady-state inactivation, or rate of recovery from inactivation of Na+ currents. In both VP and OT neurons, the macroscopic inactivation of the Na+ currents was best fitted with a double-exponential expression suggesting two rates of inactivation. Also in both types, the time course of recovery from inactivation proceeded with fast and slow time constants averaging around 8 and 350 ms, respectively, suggesting the presence of multiple pathways of recovery from inactivation. The slower time constant of recovery of inactivation may be involved in the decrease in action potential (AP) amplitude that occurs after the first spike during burst firing in both neuronal types. The larger amplitude of Na+ currents in VP vs. OT neurons may explain the previous observations that VP neurons exhibit a lower AP threshold and greater AP amplitude than OT neurons, and may serve to differently tune the firing properties and responses to neuromodulators of the respective neuronal types.

The TTX metabolite 4,9-anhydro-TTX is a highly specific blocker of the Nav1.6 voltage-dependent sodium channel

2007 ◽  
Vol 293 (2) ◽  
pp. C783-C789 ◽  
Author(s):  
Christian Rosker ◽  
Birgit Lohberger ◽  
Doris Hofer ◽  
Bibiane Steinecker ◽  
Stefan Quasthoff ◽  
...  
Keyword(s):  
Steady State ◽  
Sodium Channels ◽  
Therapeutic Intervention ◽  
Time Course ◽  
Specific Interaction ◽  
Xenopus Laevis Oocytes ◽  
Recovery From Inactivation ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Invaluable Tool

The blocking efficacy of 4,9-anhydro-TTX (4,9-ah-TTX) and TTX on several isoforms of voltage-dependent sodium channels, expressed in Xenopus laevis oocytes, was tested (Nav1.2, Nav1.3, Nav1.4, Nav1.5, Nav1.6, Nav1.7, and Nav1.8). Generally, TTX was 40–231 times more effective, when compared with 4,9-ah-TTX, on a given isoform. An exception was Nav1.6, where 4,9-ah-TTX in nanomole per liter concentrations sufficed to result in substantial block, indicating that 4,9-ah-TTX acts specifically at this peculiar isoform. The IC50 values for TTX/4,9-ah-TTX were as follows (in nmol/l): 7.8 ± 1.3/1,260 ± 121 (Nav1.2), 2.8 ± 2.3/341 ± 36 (Nav1.3), 4.5 ± 1.0/988 ± 62 (Nav1.4), 1,970 ± 565/78,500 ± 11,600 (Nav1.5), 3.8 ± 1.5/7.8 ± 2.3 (Nav1.6), 5.5 ± 1.4/1,270 ± 251 (Nav1.7), and 1,330 ± 459/>30,000 (Nav1.8). Analysis of approximal half-maximal doses of both compounds revealed minor effects on voltage-dependent activation only, whereas steady-state inactivation was shifted to more negative potentials by both TTX and 4,9-ah-TTX in the case of the Nav1.6 subunit, but not in the case of other TTX-sensitive ones. TTX shifted steady-state inactivation also to more negative potentials in case of the TTX-insensitive Nav1.5 subunit, where it also exerted profound effects on the time course of recovery from inactivation. Isoform-specific interaction of toxins with ion channels is frequently observed in the case of proteinaceous toxins. Although the sensitivity of Nav1.1 to 4,9-ah-TTX is not known, here we report evidence on a highly isoform-specific TTX analog that may well turn out to be an invaluable tool in research for the identification of Nav1.6-mediated function, but also for therapeutic intervention.

scholarly journals Distance- and activity-dependent modulation of spike back-propagation in layer V pyramidal neurons of the medial entorhinal cortex

2011 ◽  
Vol 105 (3) ◽  
pp. 1372-1379 ◽  
Author(s):  
Sonia Gasparini
Keyword(s):  
Entorhinal Cortex ◽  
High Speed ◽  
Pyramidal Neurons ◽  
Back Propagation ◽  
Medial Entorhinal Cortex ◽  
Type K ◽  
Whole Cell Patch Clamp ◽  
Voltage Dependent ◽  
Layer V ◽  
Activity Dependent

Layer V principal neurons of the medial entorhinal cortex receive the main hippocampal output and relay processed information to the neocortex. Despite the fundamental role hypothesized for these neurons in memory replay and consolidation, their dendritic features are largely unknown. High-speed confocal and two-photon Ca2+ imaging coupled with somatic whole cell patch-clamp recordings were used to investigate spike back-propagation in these neurons. The Ca2+ transient associated with a single back-propagating action potential was considerably smaller at distal dendritic locations (>200 μm from the soma) compared with proximal ones. Perfusion of Ba2+ (150 μM) or 4-aminopyridine (2 mM) to block A-type K+ currents significantly increased the amplitude of the distal, but not proximal, Ca2+ transients, which is strong evidence for an increased density of these channels at distal dendritic locations. In addition, the Ca2+ transients decreased with each subsequent spike in a 20-Hz train; this activity-dependent decrease was also more prominent at more distal locations and was attenuated by the perfusion of the protein kinase C activator phorbol-di-acetate. These data are consistent with a phosphorylation-dependent control of back-propagation during trains of action potentials, attributable mainly to an increase in the time constant of recovery from voltage-dependent inactivation of dendritic Na+ channels. In summary, dendritic Na+ and A-type K+ channels control spike back-propagation in layer V entorhinal neurons. Because the activity of these channels is highly modulated, the extent of the dendritic Ca2+ influx is as well, with important functional implications for dendritic integration and associative synaptic plasticity.

scholarly journals Inactivation of batrachotoxin-modified Na+ channels in GH3 cells. Characterization and pharmacological modification.

1992 ◽  
Vol 99 (1) ◽  
pp. 1-20 ◽  
Author(s):  
G K Wang ◽  
S Y Wang
Keyword(s):  
Time Course ◽  
Cell Voltage ◽  
Gh3 Cells ◽  
Na Channel ◽  
Na Channels ◽  
H Infinity ◽  
Recovery From Inactivation ◽  
Na Currents ◽  
Steady State Inactivation ◽  
Pharmacological Modification

Batrachotoxin (BTX)-modified Na+ currents were characterized in GH3 cells with a reversed Na+ gradient under whole-cell voltage clamp conditions. BTX shifts the threshold of Na+ channel activation by approximately 40 mV in the hyperpolarizing direction and nearly eliminates the declining phase of Na+ currents at all voltages, suggesting that Na+ channel inactivation is removed. Paradoxically, the steady-state inactivation (h infinity) of BTX-modified Na+ channels as determined by a two-pulse protocol shows that inactivation is still present and occurs maximally near -70 mV. About 45% of BTX-modified Na+ channels are inactivated at this voltage. The development of inactivation follows a sum of two exponential functions with tau d(fast) = 10 ms and tau d(slow) = 125 ms at -70 mV. Recovery from inactivation can be achieved after hyperpolarizing the membrane to voltages more negative than -120 mV. The time course of recovery is best described by a sum of two exponentials with tau r(fast) = 6.0 ms and tau r(slow) = 240 ms at -170 mV. After reaching a minimum at -70 mV, the h infinity curve of BTX-modified Na+ channels turns upward to reach a constant plateau value of approximately 0.9 at voltages above 0 mV. Evidently, the inactivated, BTX-modified Na+ channels can be forced open at more positive potentials. The reopening kinetics of the inactivated channels follows a single exponential with a time constant of 160 ms at +50 mV. Both chloramine-T (at 0.5 mM) and alpha-scorpion toxin (at 200 nM) diminish the inactivation of BTX-modified Na+ channels. In contrast, benzocaine at 1 mM drastically enhances the inactivation of BTX-modified Na+ channels. The h infinity curve reaches minimum of less than 0.1 at -70 mV, indicating that benzocaine binds preferentially with inactivated, BTX-modified Na+ channels. Together, these results imply that BTX-modified Na+ channels are governed by an inactivation process.

Persistent sodium current properties in hippocampal CA1 pyramidal neurons of young and adult rats

2014 ◽  
Vol 559 ◽  
pp. 30-33 ◽  
Author(s):  
Oleksii Lunko ◽  
Dmytro Isaev ◽  
Oleksandr Maximyuk ◽  
Gleb Ivanchick ◽  
Vadym Sydorenko ◽  
...  
Keyword(s):  
Pyramidal Neurons ◽  
Sodium Current ◽  
Persistent Sodium Current ◽  
Adult Rats ◽  
Ca1 Pyramidal Neurons ◽  
Hippocampal Ca1
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