Simulation of Different Firing Patterns in Paired Spider Mechanoreceptor Neurons: The Role of Na+ Channel Inactivation

2002 ◽  
Vol 87 (3) ◽  
pp. 1363-1368 ◽  
Author(s):  
Päivi H. Torkkeli ◽  
Andrew S. French
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Sodium Current ◽  
Sense Organ ◽  
Na Channel ◽  
Electrical Behavior ◽  
Firing Patterns ◽  
Sodium Inactivation ◽  
Firing Properties ◽  
Two Parameters

The spider VS-3 slit-sense organ contains two types of primary mechanoreceptor neurons that are morphologically similar but have different electrical behavior. Type A neurons fire only one or two action potentials in response to a mechanical or electrical step of any amplitude above the threshold, whereas type B neurons fire prolonged bursts of action potentials in response to similar stimuli. Voltage-clamp studies have shown that two voltage-activated ion currents, a noninactivating potassium current and an inactivating sodium current, dominate the firing behavior. We simulated the electrical behavior of the two neuron types, using a simplified form of Hodgkin-Huxley model based on published voltage-clamp and current-clamp recordings. Changing only two parameters of sodium inactivation, the slope of the h ∞ curve and the time constant of recovery from inactivation, allowed a complete switch between the two firing patterns. Our simulations support previous evidence that sodium inactivation controls the firing properties of these neurons and indicate that two parameter changes are needed to achieve complete transformation between the two neuron types.

Electrophysiological analysis of the neurotoxic action of a funnel-web spider toxin, delta-atracotoxin-HV1a, on insect voltage-gated Na+ channels

2001 ◽  
Vol 204 (4) ◽  
pp. 711-721 ◽  
Author(s):  
F. Grolleau ◽  
M. Stankiewicz ◽  
L. Birinyi-Strachan ◽  
X.H. Wang ◽  
G.M. Nicholson ◽  
...  
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Periplaneta Americana ◽  
Repetitive Firing ◽  
Na Channel ◽  
Na Channels ◽  
Patch Clamp Technique ◽  
Voltage Gated ◽  
Web Spider ◽  
Channel Inactivation

The effects of delta-ACTX-Hv1a, purified from the venom of the funnel-web spider Hadronyche versuta, were studied on the isolated giant axon and dorsal unpaired median (DUM) neurones of the cockroach Periplaneta americana under current- and voltage-clamp conditions using the double oil-gap technique for single axons and the patch-clamp technique for neurones. In parallel, the effects of the toxin were investigated on the excitability of rat dorsal root ganglion (DRG) neurones. In both DRG and DUM neurones, delta-ACTX-Hv1a induced spontaneous repetitive firing accompanied by plateau potentials. However, in the case of DUM neurones, plateau action potentials were facilitated when the membrane was artificially hyperpolarized. In cockroach giant axons, delta-ACTX-Hv1a also produced plateau action potentials, but only when the membrane was pre-treated with 3–4 diaminopyridine. Under voltage-clamp conditions, delta-ACTX-Hv1a specifically affected voltage-gated Na+ channels in both axons and DUM neurones. Both the current/voltage and conductance/voltage curves of the delta-ACTX-Hv1a-modified inward current were shifted 10 mV to the left of control curves. In the presence of delta-ACTX-Hv1a, steady-state Na+ channel inactivation became incomplete, causing the appearance of a non-inactivating component at potentials more positive than −40 mV. The amplitude of this non-inactivating component was dependent on the holding potential. From this study, it is concluded that, in insect neurones, delta-ACTX-Hv1a mainly affects Na+ channel inactivation by a mechanism that differs slightly from that of scorpion alpha-toxins.

Actions of insect toxin and other toxins derived from the venom of the scorpion Androctonus australis on isolated giant axons of the cockroach (Periplaneta americana)

1982 ◽  
Vol 97 (1) ◽  
pp. 67-77
Author(s):  
M. Pelhate ◽  
E. Zlotkin
Keyword(s):  
Voltage Clamp ◽  
Action Potentials ◽  
Time Course ◽  
Periplaneta Americana ◽  
Sodium Current ◽  
Giant Axon ◽  
Repetitive Firing ◽  
Current Clamp ◽  
Axonal Membrane ◽  
Insect Toxin

1. Insect toxin, mammal toxins I and II and crustacean toxin were obtained from the venom of the scorpion Androctonus australis. Their effects on the isolated giant axon of the cockroach Periplaneta americana were investigated by current-clamp and voltage-clamp techniques. 2. In current-clamp conditions, mammal toxins and crustacean toxin (1.3-13 microM) induced a large prolongation of the falling phase of the evoked action potentials. Insect toxin (0.13-3.3 microM) induced a progressive slow depolarization of the membrane potential and repetitive firing of action potentials. No changes in the time-course of the action potential were induced by insect toxin. 3. In voltage-clamp conditions, mammal and crustacean toxins induced a slowing of the turn-off of the transient inward sodium current, with either no change or a small increase in the peak sodium current. Insect toxin by contrast induced an increase in the peak sodium current and a slowing of the sodium current turn-off, this effect being greatest at lower values of the clamped membrane voltage. 4. It is concluded that the repetitive activity induced by insect toxin results from a voltage-dependent modulation of sodium inactivation coupled with an increase in both the resting and active sodium permeabilities of the cockroach axonal membrane.

scholarly journals Role of sodium channel subtype in action potential generation by neocortical pyramidal neurons

2018 ◽  
Vol 115 (30) ◽  
pp. E7184-E7192 ◽  
Author(s):  
Efrat Katz ◽  
Ohad Stoler ◽  
Anja Scheller ◽  
Yana Khrapunsky ◽  
Sandra Goebbels ◽  
...  
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Sodium Current ◽  
Na Channel ◽  
Loss Of Function ◽  
Wild Type ◽  
Strong Reduction ◽  
Hyperpolarizing Shift ◽  
Neocortical Pyramidal Neurons

Neocortical pyramidal neurons express several distinct subtypes of voltage-gated Na+ channels. In mature cells, Nav1.6 is the dominant channel subtype in the axon initial segment (AIS) as well as in the nodes of Ranvier. Action potentials (APs) are initiated in the AIS, and it has been proposed that the high excitability of this region is related to the unique characteristics of the Nav1.6 channel. Knockout or loss-of-function mutation of the Scn8a gene is generally lethal early in life because of the importance of this subtype in noncortical regions of the nervous system. Using the Cre/loxP system, we selectively deleted Nav1.6 in excitatory neurons of the forebrain and characterized the excitability of Nav1.6-deficient layer 5 pyramidal neurons by patch-clamp and Na+ and Ca2+ imaging recordings. We now report that, in the absence of Nav1.6 expression, the AIS is occupied by Nav1.2 channels. However, APs are generated in the AIS, and differences in AP propagation to soma and dendrites are minimal. Moreover, the channels that are expressed in the AIS still show a clear hyperpolarizing shift in voltage dependence of activation, compared with somatic channels. The only major difference between Nav1.6-null and wild-type neurons was a strong reduction in persistent sodium current. We propose that the molecular environment of the AIS confers properties on whatever Na channel subtype is present and that some other benefit must be conferred by the selective axonal presence of the Nav1.6 channel.

Local Circuit Connections Between Hamster Laminae III and IV Dorsal Horn Neurons

2008 ◽  
Vol 99 (3) ◽  
pp. 1306-1318 ◽  
Author(s):  
Stephen P. Schneider
Keyword(s):  
Dorsal Horn ◽  
Action Potentials ◽  
Input Resistance ◽  
Postsynaptic Membrane ◽  
Target Cells ◽  
Synaptic Organization ◽  
Firing Patterns ◽  
Electrophysiological Recordings ◽  
Single Axon ◽  
Firing Properties

To better understand the role of intrinsic spinal cord circuits in the integration of mechanosensory information, we studied synaptic transmission between neurons in Rexed's laminae III–IV, a major termination zone for cutaneous mechanoreceptor afferents, using dual, simultaneous whole cell electrophysiological recordings in young hamsters. Synaptic connections were detected between 32 of 106 cell pairs (linkage probability of 0.3) and were predominantly unidirectional (91%). Inhibitory connections outnumbered excitatory connections by 2:1. Amplitude of single-axon postsynaptic potentials (PSPs) was independent of postsynaptic cell input resistance. Intracellular labeling suggested that recordings were obtained from local axon interneurons. In connected cell pairs, the percentage of presynaptic action potentials that failed to evoke a postsynaptic response was 44 ± 29%. Shape indices of PSPs suggested that synaptic contacts were widely distributed along the postsynaptic membrane. Linkage probability was unrelated to intrinsic firing properties, laminar position of the cells or the distance (<160 μm) separating them. However, PSPs in target cells following action potentials in neurons with phasic firing patterns had longer duration and lower failure rates than PSPs activated by neurons with tonic firing patterns. Thus transmission reliability at synapses between lamina III/IV interneurons overall is low, and efficacy of these connections is related to firing properties of the presynaptic cells. The observations also suggest that synaptic organization in LIII–IV is fundamentally different from the superficial dorsal horn (LI–II) where neural circuits may be composed of stereotyped units made from connections between a few functional types of neurons.

Pharmacological properties of axonal sodium channels in the cockroach Periplaneta americana L. II. Slowing of sodium current turn-off by Condylactis toxin

1979 ◽  
Vol 83 (1) ◽  
pp. 49-58
Author(s):  
M. Pelhate ◽  
B. Hue ◽  
D. B. Sattelle
Keyword(s):  
Voltage Clamp ◽  
Sodium Channels ◽  
Action Potentials ◽  
Time Course ◽  
Periplaneta Americana ◽  
Sodium Current ◽  
Peak Amplitude ◽  
Pharmacological Properties ◽  
Plateau Potential ◽  
Conductance Increase

Condylactis toxin induces a prolonged falling phase in action potentials recorded from giant axons of the cockroach Periplaneta americana L. A distinct plateau potential can be recorded in the presence of Condylactis toxin at concentrations of 0.5 mg/ml and above. In cockroach axons, voltage-clamp experiments show that Condylactis toxin acts primarily by slowing the sodium current turn-off without affecting either the time-course of the sodium conductance increase or the peak amplitude of the transient sodium current.

Basis for tetrodotoxin and lidocaine effects on action potentials in dog ventricular myocytes

1988 ◽  
Vol 254 (6) ◽  
pp. H1157-H1166 ◽  
Author(s):  
J. A. Wasserstrom ◽  
J. J. Salata
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Ventricular Myocytes ◽  
Ionic Currents ◽  
Detectable Effect ◽  
Na Channel ◽  
Na Current ◽  
Voltage Range ◽  
Purkinje Fibers ◽  
Ventricular Cells

We studied the effects of tetrodotoxin (TTX) and lidocaine on transmembrane action potentials and ionic currents in dog isolated ventricular myocytes. TTX (0.1-1 x 10(-5) M) and lidocaine (0.5-2 x 10(-5) M) decreased action potential duration, but only TTX decreased the maximum rate of depolarization (Vmax). Both TTX (1-2 x 10(-5) M) and lidocaine (2-5 x 10(-5) M) blocked a slowly inactivating toward current in the plateau voltage range. The voltage- and time-dependent characteristics of this current are virtually identical to those described in Purkinje fibers for the slowly inactivating inward Na+ current. In addition, TTX abolished the outward shift in net current at plateau potentials caused by lidocaine alone. Lidocaine had no detectable effect on the slow inward Ca2+ current and the inward K+ current rectifier, Ia. Our results indicate that 1) there is a slowly inactivating inward Na+ current in ventricular cells similar in time, voltage, and TTX sensitivity to that described in Purkinje fibers; 2) both TTX and lidocaine shorten ventricular action potentials by reducing this slowly inactivating Na+ current; 3) lidocaine has no additional actions on other ionic currents that contribute to its ability to abbreviate ventricular action potentials; and 4) although both agents shorten the action potential by the same mechanism, only TTX reduces Vmax. This last point suggests that TTX produces tonic block of Na+ current, whereas lidocaine may produce state-dependent Na+ channel block, namely, blockade of Na+ current only after Na+ channels have already been opened (inactivated-state block).

scholarly journals Zfhx3 Transcription Factor Represses the Expression of SCN5A Gene and Decreases Sodium Current Density (INa)

2021 ◽  
Vol 22 (23) ◽  
pp. 13031
Author(s):  
Marcos Rubio-Alarcón ◽  
Anabel Cámara-Checa ◽  
María Dago ◽  
Teresa Crespo-García ◽  
Paloma Nieto-Marín ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Cardiac Tissue ◽  
Sodium Current ◽  
Na Channel ◽  
Ubiquitin Protein Ligase ◽  
Endogenous Expression ◽  
Voltage Dependent ◽  
Familial Atrial Fibrillation ◽  
Cardiac Excitability ◽  
Scn5a Gene

The ZFHX3 and SCN5A genes encode the zinc finger homeobox 3 (Zfhx3) transcription factor (TF) and the human cardiac Na+ channel (Nav1.5), respectively. The effects of Zfhx3 on the expression of the Nav1.5 channel, and in cardiac excitability, are currently unknown. Additionally, we identified three Zfhx3 variants in probands diagnosed with familial atrial fibrillation (p.M1260T) and Brugada Syndrome (p.V949I and p.Q2564R). Here, we analyzed the effects of native (WT) and mutated Zfhx3 on Na+ current (INa) recorded in HL-1 cardiomyocytes. ZFHX3 mRNA can be detected in human atrial and ventricular samples. In HL-1 cardiomyocytes, transfection of Zfhx3 strongly reduced peak INa density, while the silencing of endogenous expression augmented it (from −65.9 ± 8.9 to −104.6 ± 10.8 pA/pF; n ≥ 8, p < 0.05). Zfhx3 significantly reduced the transcriptional activity of human SCN5A, PITX2, TBX5, and NKX25 minimal promoters. Consequently, the mRNA and/or protein expression levels of Nav1.5 and Tbx5 were diminished (n ≥ 6, p < 0.05). Zfhx3 also increased the expression of Nedd4-2 ubiquitin-protein ligase, enhancing Nav1.5 proteasomal degradation. p.V949I, p.M1260T, and p.Q2564R Zfhx3 produced similar effects on INa density and time- and voltage-dependent properties in WT. WT Zfhx3 inhibits INa as a result of a direct repressor effect on the SCN5A promoter, the modulation of Tbx5 increasing on the INa, and the increased expression of Nedd4-2. We propose that this TF participates in the control of cardiac excitability in human adult cardiac tissue.

Intrinsic Firing Patterns and Whisker-Evoked Synaptic Responses of Neurons in the Rat Barrel Cortex

1999 ◽  
Vol 81 (3) ◽  
pp. 1171-1183 ◽  
Author(s):  
J. Julius Zhu ◽  
Barry W. Connors
Keyword(s):  
Action Potentials ◽  
Barrel Cortex ◽  
Cell Types ◽  
Field Size ◽  
Evoked Responses ◽  
Single Neurons ◽  
Firing Patterns ◽  
Complex Spike ◽  
Intrinsic Firing ◽  
Synaptic Responses

Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex. We have used whole cell recording in the anesthetized rat to study whisker-evoked synaptic and spiking responses of single neurons in the barrel cortex. On the basis of their intrinsic firing patterns, neurons could be classified as either regular-spiking (RS) cells, intrinsically burst-spiking (IB) cells, or fast-spiking (FS) cells. Some recordings responded to current injection with a complex spike pattern characteristic of apical dendrites. All cell types had high rates of spontaneous postsynaptic potentials, both excitatory (EPSPs) and inhibitory (IPSPs). Some spontaneous EPSPs reached threshold, and these typically elicited only single action potentials in RS cells, bursts of action potentials in FS cells and IB cells, and a small, fast spike or a complex spike in dendrites. Deflection of single whiskers evoked a fast initial EPSP, a prolonged IPSP, and delayed EPSPs in all cell types. The intrinsic firing pattern of cells predicted their short-latency whisker-evoked spiking patterns. All cell types responded best to one or, occasionally, two primary whiskers, but typically 6–15 surrounding whiskers also generated significant synaptic responses. The initial EPSP had a relatively fixed amplitude and latency, and its amplitude in response to first-order surrounding whiskers was ∼55% of that induced by the primary whisker. Second- and third-order surrounding whiskers evoked responses of ∼27 and 12%, respectively. The latency of the initial EPSP was shortest for the primary whiskers, longer for surrounding whiskers, and varied with the neurons’ depth below the pia. EPSP latency was shortest in the granular layer, longer in supragranular layers, and longest in infragranular layers. The receptive field size, defined as the total number of fast EPSP-inducing whiskers, was independent of each cell’s intrinsic firing type, its subpial depth, or the whisker stimulus parameters. On average, receptive fields included >10 whiskers. Our results show that single neurons integrate rapid synaptic responses from a large proportion of the mystacial vibrissae, and suggest that the whisker-evoked responses of barrel neurons are a function of both synaptic inputs and intrinsic membrane properties.

A voltage-clamp analysis of currents underlying cyclic AMP-induced membrane modulation in isolated peptidergic neurons of Aplysia

1984 ◽  
Vol 52 (2) ◽  
pp. 340-349 ◽  
Author(s):  
L. K. Kaczmarek ◽  
F. Strumwasser
Keyword(s):  
Cell Culture ◽  
Cyclic Amp ◽  
Voltage Clamp ◽  
Cultured Cells ◽  
Sodium Current ◽  
Negative Slope ◽  
Spontaneous Discharge ◽  
Inward Current ◽  
Outward Currents ◽  
Bag Cell Neurons

A variety of chemical and electrophysiological evidence indicates that the onset of afterdischarge and the subsequent profound enhancement of spike broadening that occur in the bag cell neurons of Aplysia are related to an increase in adenosine 3',5'-monophosphate-(cAMP) dependent protein phosphorylation. We have now used a two-electrode voltage clamp to study the properties of isolated bag cell neurons in cell culture and their response to 8 benzylthio-cAMP (8BTcAMP) and N6-n-butyl 8BTcAMP. These membrane-permeant and phosphodiesterase-resistant cAMP analogs induce spontaneous discharge and spike broadening in both the intact bag cell cluster and isolated bag cell neurons in cell culture. The dominant inward current in these cultured cells was found to be the calcium current, Ica, which was abolished by Co2+ (20 mM) or Ni2+ (10 mM) and could be observed in Na+-free media. In a minority of cells (2 of 12), in normal ionic media, a transient inward current was observed that was unaffected by Co2+ and Ni2+ and probably represents a sodium current. The three characterized potassium currents, the delayed rectifying current IK, the calcium-dependent current IC, and the early transient current IA, distinguished by their differing pharmacological and voltage-activation properties, were present in all healthy cells. Three effects of the cyclic AMP analogs (0.5 mM) on the electrical properties of these cells were 1) the emergence of a region of negative slope resistance in the steady-state I-V relations, 2) a depression of the net sustained outward currents due to depolarizing commands, and 3) a marked reduction in IA. When outward currents had been largely suppressed using high concentrations of tetraethylammonium (TEA) ions (100-460 mM) no effects of the cyclic AMP analogs could be observed on peak inward currents using NA+ and Ca2+ or Ba2+ as carriers of inward current. At least part of these electrical effects of the cyclic AMP analogs could be accounted for by a depression of a delayed potassium current and the A current.

Is there a second external lidocaine binding site on mammalian cardiac cells?

1989 ◽  
Vol 257 (1) ◽  
pp. H79-H84 ◽  
Author(s):  
L. A. Alpert ◽  
H. A. Fozzard ◽  
D. A. Hanck ◽  
J. C. Makielski
Keyword(s):  
Binding Site ◽  
Cardiac Arrhythmias ◽  
Local Anesthetics ◽  
Sodium Current ◽  
Cardiac Cells ◽  
Na Channel ◽  
Functional Difference ◽  
Na Channels ◽  
Internal Perfusion ◽  
Cardiac Purkinje Cells

Lidocaine and its permanently charged analogue QX-314 block sodium current (INa) in nerve, and by this mechanism, lidocaine produces local anesthesia. When administered clinically, lidocaine prevents cardiac arrhythmias. Nerve and skeletal muscle are much more sensitive to local anesthetics when the drugs are applied inside the cell, indicating that the binding site for local anesthetics is located on the inside of those Na channels. Using a large suction pipette for voltage clamp and internal perfusion of single cardiac Purkinje cells, we demonstrate that a charged lidocaine analogue blocks INa not only when applied from the inside but also from the outside, unlike noncardiac tissue. This functional difference in heart predicts that a second local anesthetic binding site exists outside or near the outside of cardiac Na channels and emphasizes that the cardiac Na channel is different from that in nerve.

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