Multiple potassium conductances and their role in action potential repolarization and repetitive firing behavior of neonatal rat hypoglossal motoneurons

1993 ◽  
Vol 69 (6) ◽  
pp. 2150-2163 ◽  
Author(s):  
F. Viana ◽  
D. A. Bayliss ◽  
A. J. Berger
Keyword(s):  
Action Potential ◽  
Calcium Influx ◽  
Potassium Conductance ◽  
Firing Frequency ◽  
Neonatal Rat ◽  
Repetitive Firing ◽  
Firing Behavior ◽  
Hypoglossal Motoneurons ◽  
Potassium Conductances ◽  
Action Potential Repolarization

1. The role of multiple potassium conductances in action potential repolarization and repetitive firing behavior of hypoglossal motoneurons was investigated using intracellular recording techniques in a brain stem slice preparation of the neonatal rat (0-15 days old). 2. The action potential was followed by two distinct afterhyperpolarizations (AHPs). The early one was of short duration and is termed the fAHP; the later AHP was of longer duration and is termed the mAHP. The amplitudes of both AHPs were enhanced by membrane potential depolarization (further from EK). In addition, their amplitudes were reduced by high extracellular K+ concentration, suggesting that activation of potassium conductances underlies both phases of the AHP. 3. Prolongation of the action potential and blockade of the fAHP were observed after application of 1) tetraethylammonium (TEA) (1-10 mM) and 2) 4-aminopyridine (4-AP) (0.1-0.5 mM). Calcium channel blockers had little or no effect on the fAHP or action potential duration. 4. The size of the mAHP was diminished by 1) manganese, 2) lowering external Ca2+, 3) apamin, and 4) intracellular injection of ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) suggesting that influx of calcium activates the potassium conductance that underlies the mAHP. 5. The mAHP was unaffected by nifedipine (20 microM), but was strongly reduced by focal application of omega-conotoxin GVIA, suggesting that N-type calcium channels represent the major calcium influx pathway for activation of the calcium-dependent K+ conductance underlying the mAHP. 6. Repetitive firing properties were investigated by injecting long-duration depolarizing current pulses. Steady-state firing rose linearly with injected current amplitude. The slope of the firing frequency-current (f-I) relationship averaged approximately 30 Hz/nA in control conditions. Blockade of the conductance underlying the mAHP caused a marked increase in the minimal repetitive firing frequency and in the slope of the f-I plot, indicating a prominent role for the conductance underlying the mAHP in controlling repetitive firing behavior. 7. We conclude that action potential repolarization and AHPs are due to activation of pharmacologically distinct potassium conductances. Whereas repolarization of the action potential and the fAHP involves primarily a voltage-dependent, calcium-independent potassium conductance that is TEA- and 4-AP-sensitive, the mAHP requires the influx of extracellular calcium and is apamin sensitive. Activation of the calcium-activated potassium conductance greatly influences the normal repetitive firing of neonatal hypoglossal motoneurons.

Calcium conductances and their role in the firing behavior of neonatal rat hypoglossal motoneurons

1993 ◽  
Vol 69 (6) ◽  
pp. 2137-2149 ◽  
Author(s):  
F. Viana ◽  
D. A. Bayliss ◽  
A. J. Berger
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Calcium Current ◽  
Burst Firing ◽  
Neonatal Rat ◽  
High Threshold ◽  
Calcium Spikes ◽  
Firing Behavior ◽  
Hypoglossal Motoneurons ◽  
Voltage Dependent

1. The role of calcium conductances in action potential generation and repetitive firing behavior of hypoglossal motoneurons (HMs) was investigated using intracellular recording and patch-clamp techniques in a brain stem slice preparation of neonatal rats (0-15 days old). 2. The action potential was followed by an afterdepolarization (ADP). The ADP was voltage dependent, increasing with membrane hyperpolarization. Raising the extracellular Ca2+ concentration or replacing Ca2+ with Ba2+ increased the ADP amplitude, whereas replacement of Ca2+ with Mn2+ blocked it. The ADP was partially reduced by amiloride and low concentrations of Ni2+. 3. The firing behavior of individual neonatal HMs was influenced by membrane potential. From depolarized potentials, HMs fired tonically in response to a depolarizing current pulse, whereas from more hyperpolarized membrane potentials (more negative than -70 mV), a subset of HMs fired an initial burst of action potentials followed by a prolonged afterhyperpolarization and tonic firing. The incidence of burst-firing behavior was highest among young motoneurons and disappeared by the tenth postnatal day. In addition, prominent rebound depolarizations characterized the response of neonatal motoneurons to hyperpolarizing prepulses. 4. Pharmacological characterization of the rebound depolarization demonstrated that it was calcium dependent. Its amplitude was insensitive to tetrodotoxin and it was eliminated by replacement of Ca2+ with Mn2+ or addition of Ni2+. Amiloride (1-1.5 mM) had no effect on the rebound response or burst firing. 5. The presence of high-threshold calcium spikes was detected at all postnatal ages, but only after blockade of outward currents with intra- or extracellular tetraethylammonium. The high-threshold calcium spikes were greatly enhanced when Ba2+ replaced Ca2+. 6. Calcium currents of neonatal HMs were characterized in whole-cell patch-clamp recordings of thin medullary slices under conditions that minimized voltage-dependent Na+ and K+ currents. Low voltage-activated (LVA) and a high voltage-activated (HVA) calcium current components were identified on the basis of their voltage thresholds for activation, kinetics of inactivation, and pharmacological sensitivity. 7. The LVA calcium current began to activate at around -60 mV and inactivated nearly completely within 100 ms. Complete steady-state inactivation occurred at potentials more positive than -60 mV. The LVA current was selectively reduced by 1 mM amiloride (31%). 8. A larger-amplitude calcium current activated at potentials around -35 mV. Inactivation of this HVA current was slower than that of the LVA current and incomplete. About 1/3 of this current was sensitive to 1 microM omega-conotoxin GVIA, whereas a smaller fraction was blocked by 10 microM nifedipine.(ABSTRACT TRUNCATED AT 400 WORDS)

Dendrotoxin blocks accommodation in frog myelinated axons

1989 ◽  
Vol 62 (1) ◽  
pp. 174-184 ◽  
Author(s):  
M. O. Poulter ◽  
T. Hashiguchi ◽  
A. L. Padjen
Keyword(s):  
Action Potential ◽  
Computer Model ◽  
Action Potentials ◽  
Potassium Conductance ◽  
Constant Stimulus ◽  
Motor Axons ◽  
Myelinated Axons ◽  
Frequency Adaptation ◽  
Potassium Conductances ◽  
Slow Potassium

1. Intracellular microelectrode recordings from large sensory and motor myelinated axons in spinal roots of Rana pipiens were used to study the effects of dendrotoxin (DTX), a specific blocker of a fast activating potassium current (GKf1). 2. Dendrotoxin reduced the ability of myelinated sensory and motor axons to accommodate to a constant stimulus. A depolarizing current step, which normally evoked only one action potential, after dendrotoxin treatment (200-500 nM) produced a train of action potentials. These spike trains lasted 29 +/- 2.8 (SE) ms on average in sensory fibers (n = 18) and 40.2 +/- 4.5 ms in motor fibers (n = 9). 3. After dendrotoxin treatment, in addition to a reduction in the ability to accommodate to a constant stimulus, a slowing in the rate of action potential generation was evident (spike frequency adaptation). 4. Dendrotoxin had no effect on the rising phase of conducted action potentials evoked by peripheral stimulation. Together with a lack of effect on the absolute refractory period, these results indicate that dendrotoxin does not affect sodium channel activity. 5. The steady-state voltage/current relationship was unchanged in response to hyperpolarizing current pulses; however, there was a significant increase in cord resistance in response to depolarizing current steps, demonstrating that DTX decreases outward rectification. 6. A computer model based on Hodgkin and Huxley equations was developed, which included the three voltage-dependent potassium conductances described by Dubois. The model reproduced major experimental results: removal of the conductance, termed GKf1, reduced the accommodation in the early phase of a continuous stimulus, indicating that this current could be responsible for the early accommodation. The hypothesis that the slow potassium conductance GKs regulates late accommodation and action potential frequency adaptation is also supported by the computer model. 7. In summary, these results suggest that in amphibian myelinated sensory and motor axons, the activity of potassium conductances can account for accommodation and adaptation without involvement of sodium conductance activity.

scholarly journals A Mathematical Model for the Cardiac Action Potential Based on Slow Inactivation of Sodium Conductance

1968 ◽  
Vol 21 (1) ◽  
pp. 37 ◽  
Author(s):  
L Munk ◽  
E PGeorge
Keyword(s):  
Mathematical Model ◽  
Action Potential ◽  
Action Potentials ◽  
Sodium Current ◽  
Potassium Conductance ◽  
Slow Inactivation ◽  
Squid Axon ◽  
Purkinje Fibres ◽  
Cardiac Action ◽  
Potassium Conductances

A mathematical model for the action potential in Purkinje fibres is developed. It is based on voltage-clamp results which show that inactivation of sodium current in these muscles is much slower than in squid axon and that the latent rise in potassium conductance is not present. Both the sodium and the potassium conductances are represented as a sum of slow and fast components. This is incorporated in the suitably adjusted Hodgkin-Huxley model for the squid axon. It is shown that such a model can account satisfactorily for the shape of the action potentials in Purkinje fibres.

Resilient RTN Fast Spiking in Kv3.1 Null Mice Suggests Redundancy in the Action Potential Repolarization Mechanism

2002 ◽  
Vol 87 (3) ◽  
pp. 1303-1310 ◽  
Author(s):  
Darrell M. Porcello ◽  
Chi Shun Ho ◽  
Rolf H. Joho ◽  
John R. Huguenard
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Action Potentials ◽  
Brain Slices ◽  
Firing Frequency ◽  
Wild Type ◽  
Genetic Redundancy ◽  
Fast Spiking ◽  
Deficient Mice ◽  
Action Potential Repolarization

Fast spiking (FS), GABAergic neurons of the reticular thalamic nucleus (RTN) are capable of firing high-frequency trains of brief action potentials, with little adaptation. Studies in recombinant systems have shown that high-voltage-activated K+ channels containing the Kv3.1 and/or Kv3.2 subunits display biophysical properties that may contribute to the FS phenotype. Given that RTN expresses high levels of Kv3.1, with little or no Kv3.2, we tested whether this subunit was required for the fast action potential repolarization mechanism essential to the FS phenotype. Single- and multiple-action potentials were recorded using whole-cell current clamp in RTN neurons from brain slices of wild-type and Kv3.1-deficient mice. At 23°C, action potentials recorded from homozygous Kv3.1 deficient mice (Kv3.1−/−) compared with their wild-type (Kv3.1+/+) counterparts had reduced amplitudes (−6%) and fast after-hyperpolarizations (−16%). At 34°C, action potentials in Kv3.1−/− mice had increased duration (21%) due to a reduced rate of repolarization (−30%) when compared with wild-type controls. Action potential trains in Kv3.1−/− were associated with a significantly greater spike decrement and broadening and a diminished firing frequency versus injected current relationship ( F/I) at 34°C. There was no change in either spike count or maximum instantaneous frequency during low-threshold Ca2+ bursts in Kv3.1−/− RTN neurons at either temperature tested. Our findings show that Kv3.1 is not solely responsible for fast spikes or high-frequency firing in RTN neurons. This suggests genetic redundancy in the system, possibly in the form of other Kv3 members, which may suffice to maintain the FS phenotype in RTN neurons in the absence of Kv3.1.

Low-Voltage-Activated Calcium Current Does Not Regulate the Firing Behavior in Paired Mechanosensory Neurons With Different Adaptation Properties

2000 ◽  
Vol 83 (2) ◽  
pp. 746-753 ◽  
Author(s):  
Shin-Ichi Sekizawa ◽  
Andrew S. French ◽  
Päivi H. Torkkeli
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Low Voltage ◽  
Firing Frequency ◽  
Oscillatory Behavior ◽  
Firing Behavior ◽  
Single Action ◽  
Synaptic Excitation ◽  
Intracellular Ca ◽  
The Difference

Low-voltage-activated Ca2+ currents (LVA- I Ca) are believed to perform several roles in neurons such as lowering the threshold for action potentials, promoting burst firing and oscillatory behavior, and enhancing synaptic excitation. They also may allow rapid increases in intracellular Ca2+ concentration. We discovered LVA- I Ca in both members of paired mechanoreceptor neurons in a spider, where one neuron adapts rapidly (Type A) and the other slowly (Type B) in response to a step stimulus. To learn if I Ca contributed to the difference in adaptation behavior, we studied the kinetics of I Ca from isolated somata under single-electrode voltage-clamp and tested its physiological function under current clamp. LVA- I Ca was large enough to fire single action potentials when all other voltage-activated currents were blocked, but we found no evidence that it regulated firing behavior. LVA- I Ca did not lower the action potential threshold or affect firing frequency. Previous experiments have failed to find Ca2+-activated K+ current ( I K(Ca)) in the somata of these neurons, so it is also unlikely that LVA- I Ca interacts with I K(Ca) to produce oscillatory behavior. We conclude that LVA-Ca2+ channels in the somata, and possible in the dendrites, of these neurons open in response to the depolarization caused by receptor current and by the voltage-activated Na+ current ( I Na) that produces action potential(s). However, the role of the increased intracellular Ca2+ concentration in neuronal function remains enigmatic.

Development of Potassium Conductances in Perinatal Rat Phrenic Motoneurons

2000 ◽  
Vol 83 (6) ◽  
pp. 3497-3508 ◽  
Author(s):  
Miguel Martin-Caraballo ◽  
John J. Greer
Keyword(s):  
Action Potential ◽  
Potassium Currents ◽  
Perinatal Period ◽  
Repetitive Firing ◽  
Respiratory Drive ◽  
Calcium Dependent ◽  
Phrenic Motoneurons ◽  
Potential Shape ◽  
Potassium Conductances ◽  
Firing Properties

Prior to the inception of inspiratory synaptic drive transmission from medullary respiratory centers, rat phrenic motoneurons (PMNs) have action potential and repetitive firing characteristics typical of immature embryonic motoneurons. During the period spanning from when respiratory bulbospinal and segmental afferent synaptic connections are formed at embryonic day 17 ( E17) through to birth (gestational period is ∼21 days), a pronounced transformation of PMN electrophysiological properties occurs. In this study, we test the hypothesis that the elaboration of action potential afterpotentials and the resulting changes in repetitive firing properties are due in large part to developmental changes in PMN potassium conductances. Ionic conductances were measured via whole cell patch recordings using a cervical slice-phrenic nerve preparation isolated from perinatal rats. Voltage- and current-clamp recordings revealed that PMNs expressed outward rectifier ( I KV) and A-type potassium currents that regulated PMN action potential and repetitive firing properties throughout the perinatal period. There was an age-dependent leftward shift in the activation voltage and a decrease in the time-to-peak of I KV during the period from E16 through to birth. The most dramatic change during the perinatal period was the increase in calcium-activated potassium currents after the inception of inspiratory drive transmission at E17. Block of the maxi-type calcium-dependent potassium conductance caused a significant increase in action potential duration and a suppression of the fast afterhyperpolarizing potential. Block of the small conductance calcium-dependent potassium channels resulted in a marked suppression of the medium afterhyperpolarizing potential and an increase in the repetitive firing frequency. In conclusion, the increase in calcium-mediated potassium conductances are in large part responsible for the marked transformation in action potential shape and firing properties of PMNs from the time between the inception of fetal respiratory drive transmission and birth.

Reconstruction of hippocampal CA1 pyramidal cell electrophysiology by computer simulation

1994 ◽  
Vol 71 (6) ◽  
pp. 2033-2045 ◽  
Author(s):  
E. N. Warman ◽  
D. M. Durand ◽  
G. L. Yuen
Keyword(s):  
Action Potential ◽  
Voltage Clamp ◽  
Pyramidal Cell ◽  
Compartment Model ◽  
Ionic Channels ◽  
Firing Frequency ◽  
Repetitive Firing ◽  
Amplitude Increase ◽  
Voltage Dependent ◽  
K Current

1. We have developed a 16-compartment model that reproduces most of the features of the CA1 pyramidal cell electrophysiology observed experimentally. The model was constructed using seven active ionic conductances: gNa, gCa, gDR, gCT, gA, gM, and gAHP whose kinetics have been, inferred, in most cases, from the available voltage-clamp data obtained from these cells. We focussed the simulation on the initial and late accommodation, the slow depolarization potential and the spike broadening during repetitive firing, because their mechanisms are not well understood. 2. Current-clamp records were reproduced by iterative adjustments to the ionic maximum conductances, scaling and/or “reshaping” of the gates' time constant within the experimental voltage-clamp data, and shifting the position of the steady-state gate opening. The final properties of the ionic channels were not significantly different from the voltage-clamp experiments. 3. The resulting model reproduces all four after-potentials that have been recorded to follow activation of the cell. The fast, medium, and slow after-hyperpolarization potentials (AHPs) were, respectively, generated by ICT, IM, and IAHP. Furthermore, the model suggests that the mechanisms underlying the depolarization after potential (DAP) is mostly due to passive recharging of the soma by the dendrites. 4. The model also reproduces most of the firing features experimentally observed during injection of long current pulses. Model responses showed a small initial decrease in the firing frequency during a slow underlying depolarization potential, followed by a more significant frequency decrease. Moreover, a gradual broadening of the action potential and loss of the fast AHP were also observed during the initial high-frequency firing, followed, as the firing frequency decreased, by a gradual recovery of the spikes' original width and fast AHP amplitude increase. 5. A large reduction of the K repolarizing current was required to reproduce the spike broadening and reduction of the fast AHP experimentally observed in CA1 cells during repetitive firing responses. The incorporation of a transient Ca- and voltage-dependent K current (ICT) into the model successfully reproduced these experimental observations. In contrast, we were unable to reproduce this phenomenon when a large persistent Ca- and voltage-dependent K current (generally named IC) was included in the model. These results suggest that there is a strong contribution to action-potential repolarization and fast AHP by a transient Ca- and voltage-dependent K current (ICT). 6. The two accommodation steps were induced by a progressively enlargement of two K currents IM (initial) and IAHP (late).(ABSTRACT TRUNCATED AT 400 WORDS)

Ionic Current Model of a Hypoglossal Motoneuron

2005 ◽  
Vol 93 (2) ◽  
pp. 723-733 ◽  
Author(s):  
Liston K. Purvis ◽  
Robert J. Butera
Keyword(s):  
Action Potential ◽  
Current Model ◽  
Ionic Current ◽  
Input Resistance ◽  
Ionic Currents ◽  
Neonatal Rat ◽  
Repetitive Firing ◽  
Hypoglossal Motoneuron ◽  
Age Dependent ◽  
Firing Properties

We have developed a single-compartment, electrophysiological, hypoglossal motoneuron (HM) model based primarily on experimental data from neonatal rat HMs. The model is able to reproduce the fine features of the HM action potential: the fast afterhyperpolarization, the afterdepolarization, and the medium-duration afterhyperpolarization (mAHP). The model also reproduces the repetitive firing properties seen in neonatal HMs and replicates the neuron's response to pharmacological experiments. The model was used to study the role of specific ionic currents in HM firing and how variations in the densities of these currents may account for age-dependent changes in excitability seen in HMs. By varying the density of a fast inactivating calcium current, the model alternates between accelerating and adapting firing patterns. Modeling the age-dependent increase in H current density accounts for the decrease in mAHP duration observed experimentally, but does not fully account for the decrease in input resistance. An increase in the density of the voltage-dependent potassium currents and the H current is required to account for the decrease in input resistance. These changes also account for the age-dependent decrease in action potential duration.

scholarly journals Pharmacology of currents underlying the different firing patterns of spinal sensory neurons and interneurons identified in vivo using multivariate analysis

2011 ◽  
Vol 105 (5) ◽  
pp. 2487-2500 ◽  
Author(s):  
Crawford I. P. Winlove ◽  
Alan Roberts
Keyword(s):  
Action Potential ◽  
Potassium Channel ◽  
Firing Frequency ◽  
Repetitive Firing ◽  
Channel Blockers ◽  
Drug Induced ◽  
Firing Patterns ◽  
Single Action ◽  
Single Action Potential

The operation of neuronal networks depends on the firing patterns of the network's neurons. When sustained current is injected, some neurons in the central nervous system fire a single action potential and others fire repetitively. For example, in Xenopus laevis tadpoles, primary-sensory Rohon-Beard (RB) neurons fired a single action potential in response to 300-ms rheobase current injections, whereas dorsolateral (DL) interneurons fired repetitively at 10–20 Hz. To investigate the basis for these differences in vivo, we examined drug-induced changes in the firing patterns of Xenopus spinal neurons using whole cell current-clamp recordings. Neuron types were initially separated through cluster analysis, and we compared results produced using different clustering algorithms. We used these results to develop a predictive function to classify subsequently recorded neurons. The potassium channel blocker tetraethylammonium (TEA) converted single-firing RB neurons to low-frequency repetitive firing but reduced the firing frequency of repetitive-firing DL interneurons. Firing frequency in DL interneurons was also reduced by the potassium channel blockers 4-aminopyridine (4-AP), catechol, and margatoxin; 4-AP had the greatest effect. The calcium channel blockers amiloride and nimodipine had few effects on firing in either neuron type but reduced action potential duration in DL interneurons. Muscarine, which blocks M-currents, did not affect RB neurons but reduced firing frequency in DL interneurons. These results suggest that potassium currents may control neuron firing patterns: a TEA-sensitive current prevents repetitive firing in RB neurons, whereas a 4-AP-sensitive current underlies repetitive firing in DL interneurons. The cluster and discriminant analysis described could help to classify neurons in other systems.

Sign in / Sign up

Export Citation Format

Share Document