On the Persistent Sodium Current in Squid Giant Axons

2003 ◽  
Vol 89 (1) ◽  
pp. 640-644 ◽  
Author(s):  
John R. Clay
Keyword(s):  
Ion Channel ◽  
Sodium Current ◽  
Persistent Current ◽  
Sodium Ion ◽  
Ion Current ◽  
Peak Amplitude ◽  
Potential Range ◽  
Slow Inactivation ◽  
Giant Axons ◽  
Low Threshold

R. F. Rakowski, D. C. Gadsby, and P. DeWeer have reported a persistent, tetrodotoxin-sensitive sodium ion current ( I NaP) in squid giant axons having a low threshold (-90 mV) and a maximal inward amplitude of −4 μA/cm2 at −50 mV. This report makes the case that most of I NaP is attributable to an ion channel mechanism distinct from the classical rapidly activating and inactivating sodium ion current, I Na, which is also tetrodotoxin sensitive. The analysis of the contribution of I Na to I NaP is critically dependent on slow inactivation of I Na. The results of this gating process reported here demonstrate that inactivation of I Na is complete in the steady-state for V > −40 mV, thereby making it unlikely that I NaP in this potential range is attributable to I Na. Moreover, −90 mV is well below I Na threshold, as demonstrated by the C. A. Vandenberg and F. Bezanilla model of I Na gating in squid giant axons. Their model predicts a persistent current having a threshold of −60 mV and a peak amplitude of −25 μA/cm2 at −20 mV. Modulation of this component by the slow inactivation process predicts a persistent current that is finite in the −60- to −40-mV range having a peak amplitude of −1μA/cm-2 at −50 mV. Subtraction of this current from the I NaP measurements yields the portion of INaP that appears to be attributable to an ion channel mechanism distinct from I Na.

scholarly journals Low-Threshold, Persistent Sodium Current in Rat Large Dorsal Root Ganglion Neurons in Culture

1997 ◽  
Vol 77 (3) ◽  
pp. 1503-1513 ◽  
Author(s):  
Mark D. Baker ◽  
Hugh Bostock
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Sodium Current ◽  
Threshold Current ◽  
Persistent Current ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Large Neurons

Baker, Mark D. and Hugh Bostock. Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture. J. Neurophysiol. 77: 1503–1513, 1997. Dorsal root ganglion neurons from adult rats (≥200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50–75 μm apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to −35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to −70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least −70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.

scholarly journals Characterization of Direct Perturbations on Voltage-Gated Sodium Current by Esaxerenone, a Nonsteroidal Mineralocorticoid Receptor Blocker

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 549
Author(s):  
Wei-Ting Chang ◽  
Sheng-Nan Wu
Keyword(s):  
Mineralocorticoid Receptor ◽  
Sodium Current ◽  
Ionic Currents ◽  
Antagonistic Effect ◽  
Gh3 Cells ◽  
Excitable Cells ◽  
Voltage Gated ◽  
Ic50 Value ◽  
Low Threshold

Esaxerenone (ESAX; CS-3150, Minnebro®) is known to be a newly non-steroidal mineralocorticoid receptor (MR) antagonist. However, its modulatory actions on different types of ionic currents in electrically excitable cells remain largely unanswered. The present investigations were undertaken to explore the possible perturbations of ESAX on the transient, late and persistent components of voltage-gated Na+ current (INa) identified from pituitary GH3 or MMQ cells. GH3-cell exposure to ESAX depressed the transient and late components of INa with varying potencies. The IC50 value of ESAX required for its differential reduction in peak or late INa in GH3 cells was estimated to be 13.2 or 3.2 μM, respectively. The steady-state activation curve of peak INa remained unchanged during exposure to ESAX; however, recovery of peak INa block was prolonged in the presence 3 μM ESAX. In continued presence of aldosterone (10 μM), further addition of 3 μM ESAX remained effective at inhibiting INa. ESAX (3 μM) potently reversed Tef-induced augmentation of INa. By using isosceles-triangular ramp pulse with varying durations, the amplitude of persistent INa measured at high or low threshold was enhanced by the presence of tefluthrin (Tef), in combination with the appearance of the figure-of-eight hysteretic loop; moreover, hysteretic strength of the current was attenuated by subsequent addition of ESAX. Likewise, in MMQ lactotrophs, the addition of ESAX also effectively decreased the peak amplitude of INa along with the increased current inactivation rate. Taken together, the present results provide a noticeable yet unidentified finding disclosing that, apart from its antagonistic effect on MR receptor, ESAX may directly and concertedly modify the amplitude, gating properties and hysteresis of INa in electrically excitable cells.

Subthreshold frequency selectivity in avian auditory thalamus

1994 ◽  
Vol 71 (4) ◽  
pp. 1361-1372 ◽  
Author(s):  
B. Strohmann ◽  
D. W. Schwarz ◽  
E. Puil
Keyword(s):  
Frequency Selectivity ◽  
Membrane Properties ◽  
Resting Potential ◽  
Resonant Peak ◽  
Auditory Signal ◽  
Voltage Response ◽  
Potential Range ◽  
Na Current ◽  
Frequency Responses ◽  
Low Threshold

1. We studied the frequency responses of neurons in the nucleus ovoidalis (OV), the principal thalamic auditory relay nucleus of the chicken, in the subthreshold range of membrane potentials. The frequency response is the impedance amplitude profile evident in the voltage response to a broadband stimulus. The stimulus was a deterministic periodic current input of small amplitude, sweeping through a specified frequency range. We used whole-cell, tight-seal recording techniques in slices to study the voltage responses and membrane properties in current and voltage clamp. 2. Generally, low-frequency resonant humps with peak impedances of approximately 6 Hz characterized the frequency responses of OV neurons. This resonance was the principal determinant for frequency selectivity in the majority of OV neurons expressing only a tonic mode of firing. 3. The 6-Hz resonance was voltage dependent and most distinct where the activation ranges of a hyperpolarization activated inward current (IH) and a persistent Na+ current tend to overlap. The potential range for optimal resonance often included the resting potential. 4. Application of the Na+ current antagonist, tetrodotoxin, blocked the persistent Na+ current and most of the resonant hump at depolarized levels but did not affect the resonant peak along the frequency axis. Thus the persistent Na+ current may serve to amplify the resonance. 5. Extracellular application of Cs+, but not Ba2+, blocked a voltage sag during pulsed hyperpolarization as well as the IH current. Application of Cs+ also eliminated the 6-Hz resonance. An IH seems, therefore, instrumental for the resonance. 6. A minority of neurons that expressed low-threshold Ca2+ spikes and burst firing at hyperpolarized states displayed voltage oscillations at 2-4 Hz, spontaneously or in response to pulsatile stimuli. Application of Ni2+ blocked the oscillations and the low-threshold spikes, presumably produced by a T-type Ca2+ current. The resonance at 6 Hz, however, was only slightly affected by Ni2+. A T-type current, therefore, is critical for the 2- to 4-Hz oscillations. 7. Membrane resonance may dominate the power spectrum of subthreshold potential fluctuations. The resonance demonstrated in vitro may be stabilized by experimental procedures; its frequency may be different and more variable in vivo. Resonances in thalamic neurons may play a role in auditory signal processing in birds.

scholarly journals De Novo Synthesis of Modified Saxitoxins for Sodium Ion Channel Study

2009 ◽  
Vol 131 (35) ◽  
pp. 12524-12525 ◽  
Author(s):  
Brian M. Andresen ◽  
J. Du Bois
Keyword(s):  
Ion Channel ◽  
De Novo ◽  
Sodium Ion ◽  
De Novo Synthesis

scholarly journals The Piezo2 ion channel is mechanically activated by low-threshold positive pressure

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kyung Chul Shin ◽  
Hyun Ji Park ◽  
Jae Gon Kim ◽  
In Hwa Lee ◽  
Hawon Cho ◽  
...  
Keyword(s):  
Ion Channel ◽  
Positive Pressure ◽  
Low Threshold

scholarly journals Sinusoidal voltage protocols for rapid characterisation of ion channel kinetics

2017 ◽  
Author(s):  
Kylie A. Beattie ◽  
Adam P. Hill ◽  
Rémi Bardenet ◽  
Yi Cui ◽  
Jamie I. Vandenberg ◽  
...  
Keyword(s):  
Ion Channel ◽  
Voltage Clamp ◽  
Ion Current ◽  
Ion Currents ◽  
Channel Kinetics ◽  
Sinusoidal Voltage ◽  
Square Wave ◽  
Voltage Clamps ◽  
Ion Channel Kinetics ◽  
Cell Cell

AbstractUnderstanding the roles of ion currents is crucial to predict the action of pharmaceuticals and mutations in different scenarios, and thereby to guide clinical interventions in the heart, brain and other electrophysiological systems. Our ability to predict how ion currents contribute to cellular electrophysiology is in turn critically dependent on our characterisation of ion channel kinetics — the voltage-dependent rates of transition between open, closed and inactivated channel states. We present a new method for rapidly exploring and characterising ion channel kinetics, applying it to the hERG potassium channel as an example, with the aim of generating a quantitatively predictive representation of the ion current. We fit a mathematical model to currents evoked by a novel 8 second sinusoidal voltage clamp in CHO cells over-expressing hERG1a. The model is then used to predict over 5 minutes of recordings in the same cell in response to further protocols: a series of traditional square step voltage clamps, and also a novel voltage clamp comprised of a collection of physiologically-relevant action potentials. We demonstrate that we can make predictive cell-specific models that outperform the use of averaged data from a number of different cells, and thereby examine which changes in gating are responsible for cell-cell variability in current kinetics. Our technique allows rapid collection of consistent and high quality data, from single cells, and produces more predictive mathematical ion channel models than traditional approaches.Table of Contents CategoryTechniques for Physiology1Key PointsIon current kinetics are commonly represented by current-voltage relationships, time-constant voltage relationships, and subsequently mathematical models fitted to these. These experiments take substantial time which means they are rarely performed in the same cell.Rather than traditional square-wave voltage clamps, we fit a model to the current evoked by a novel sum-of-sinusoids voltage clamp that is only 8 seconds long.Short protocols that can be performed multiple times within a single cell will offer many new opportunities to measure how ion current kinetics are affected by changing conditions.The new model predicts the current under traditional square-wave protocols well, with better predictions of underlying currents than literature models. The current under a novel physiologically-relevant series of action potential clamps is predicted extremely well.The short sinusoidal protocols allow a model to be fully fitted to individual cells, allowing us to examine cell-cell variability in current kinetics for the first time.

Anterior pituitary control of active sodium transport across frog skin

1961 ◽  
Vol 200 (3) ◽  
pp. 444-450 ◽  
Author(s):  
R. M. Myers ◽  
W. R. Bishop ◽  
B. T. Scheer
Keyword(s):  
Sodium Transport ◽  
Rana Pipiens ◽  
Sodium Current ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Anterior Lobe ◽  
Sodium Ion ◽  
Resting Potential ◽  
Active Sodium ◽  
Active Sodium Transport

Removal of the anterior lobe of the pituitary from the frog Rana pipiens is followed by an increase in the outflux of Na22 across the skin, which persists at least 4 months, and by a decrease in resting potential and sodium (‘short-circuit’) current, which persists no more than 3 weeks. The increased outflux is interpreted as resulting from increased permeability of the skin to sodium ion, and the decreased sodium current is interpreted as a decreased rate of active sodium transport. Either change is opposed by treatment with mammalian ACTH or with aldosterone. Effects of other hormones could not be established with certainty. The increased permeability of the skin to sodium appears to be associated with a decrease in the amount of a mucopolysaccharide in the dermis. The evidence suggests that the pituitary effects involve the interrenal bodies.

Differences in voltage-dependent sodium currents exhibited by superficial and deep layer neurons of guinea pig entorhinal cortex

1994 ◽  
Vol 71 (5) ◽  
pp. 1986-1991 ◽  
Author(s):  
S. Fan ◽  
M. Stewart ◽  
R. K. Wong
Keyword(s):  
Guinea Pig ◽  
Entorhinal Cortex ◽  
Deep Layer ◽  
Sodium Current ◽  
Membrane Conductance ◽  
Cell Voltage ◽  
Superficial Layer ◽  
Peak Amplitude ◽  
Sodium Currents ◽  
Test Pulse

1. Sodium currents were studied using whole-cell voltage-clamp techniques in neurons acutely isolated from superficial (II/III) and deep (V/VI) layers of guinea pig entorhinal cortex. 2. Sodium currents were larger (peak amplitude) in superficial than in deep layer cells under the same conditions: -1939 +/- 780 (SD) pA (N = 6) versus -307 +/- 257 pA (N = 6). Specific membrane conductance was calculated to be 12.3 +/- 9.6 mS/cm2 for superficial layer cells and 1.4 +/- 0.9 mS/cm2 for deep layer cells. 3. Sodium currents could be activated in superficial layer cells from potentials as depolarized as -20 mV, whereas no significant currents could be activated in deep neurons from potentials more depolarized than about -50 mV. Using a protocol consisting of a 25-ms prepulse and a 20 ms test pulse, the inactivation curves for superficial layer cells were found to be shifted toward more depolarized potentials by an average of 15 mV (V50 = -59.8 +/- 3.8 mV compared with -75.7 +/- 12.0 mV for deep cells). This produced a region of overlap with the activation curves for superficial cells. 4. Over a range of about -50 to -20 mV in superficial layer cells, the region of overlap of the activation and inactivation curves, a sodium current could be activated, which did not fully inactivate during the test pulse (average peak amplitude: -89.5 +/- 48.7 pA; crossover voltage: -39.2 +/- 2.0 mV). Voltage steps to more depolarized potentials, outside the voltage “window”, permitted complete inactivation of the sodium current.(ABSTRACT TRUNCATED AT 250 WORDS)

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