scholarly journals The ionic mechanism of membrane potential oscillations and membrane resonance in striatal LTS interneurons

2016 ◽  
Vol 116 (4) ◽  
pp. 1752-1764 ◽  
Author(s):  
S. C. Song ◽  
J. A. Beatty ◽  
C. J. Wilson
Keyword(s):  
Membrane Potential ◽  
Fluorescent Protein ◽  
Calcium Currents ◽  
Biophysical Modeling ◽  
Potential Oscillation ◽  
Potential Oscillations ◽  
Striatal Slices ◽  
Voltage Range ◽  
Membrane Potential Oscillation ◽  
Membrane Resonance

Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (greater than −40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of L-type calcium currents (CaV1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (CaV2.2) reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. The blocking of any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated anoctamin 2 (ANO2), and not ANO1, as the CaCC source. Biophysical modeling showed that CaV1, CaV2.2, and ANO2 are sufficient to generate a membrane potential oscillation and membrane resonance, similar to that in LTS interneurons. LTS interneurons exhibit a membrane potential oscillation and membrane resonance that are both generated by CaV1 and CaV2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.

Synchronized oscillatory activity in leech neurons induced by calcium channel blockers

1991 ◽  
Vol 66 (6) ◽  
pp. 1858-1873 ◽  
Author(s):  
J. D. Angstadt ◽  
W. O. Friesen
Keyword(s):  
Membrane Potential ◽  
Conceptual Model ◽  
Rhythmic Activity ◽  
Oscillatory Activity ◽  
Cycle Period ◽  
Channel Blockers ◽  
Phase Point ◽  
Potential Oscillations ◽  
Membrane Potential Oscillation ◽  
Electrotonic Interactions

1. Leech ganglia were superfused with salines in which Ca2+ was replaced with equimolar concentrations of Co2+, Ni2+, or Mn2+. These salines elicited rhythmic membrane potential oscillations with cycle periods ranging from 8 to 25 s in all neurons examined within the ventral nerve cord. 2. Rhythmic activity consisted of a rapid depolarization to a prolonged (3-6 s) plateau level, followed by a rapid repolarization. Each depolarization elicited a burst of action potentials. Peak-to-trough amplitudes of the plateau depolarizations were up to 40 mV in some cells. The plateau depolarizations were separated by slowly depolarizing ramp potentials. 3. Oscillations in all neurons were synchronized (in phase) both within individual ganglia and between ganglia linked by connective nerves. Rhythmic activity in isolated ganglia persisted after the interposed connective nerves were cut. 4. The occurrence of oscillatory activity was strongly correlated with the block of chemical synaptic transmission. 5. Electrotonic interactions persisted during oscillatory activity and may be one mechanism by which oscillations are synchronized. 6. The phase of rhythmic impulse bursts monitored with extracellular electrodes could be reset by electrical stimulation of connective nerves but not by injection of current pulses into individual neurons. Phase reset appeared to occur within one cycle and to a fixed phase point (plateau termination). 7. Oscillatory activity was eliminated by 75-100% reductions of [Na+]o (Na+ replaced with N-methyl-D-glucamine). Smaller reductions of Na+ (by 25-50%) increased the cycle period of oscillations. 8. The Na(+)-K+ pump inhibitors ouabain and strophanthidin disrupted oscillations. Cells were depolarized by approximately 20 mV and fired tonically. After the initial washout of the inhibitors, cells repolarized and became quiescent. After several minutes of continued washing, oscillatory activity resumed. 9. A conceptual model is proposed to explain the mechanisms underlying oscillatory activity induced by Ca2+ channel blockers. According to this model, depolarizing plateaus are generated by a noninactivating Na+ conductance. Na+ influx during the plateau leads to an increase in [Na+]i, which activates an electrogenic Na(+)-K+ pump that contributes to plateau termination. 10. A quantitative computer simulation incorporating six types of currents (capacity, outward rectifying potassium, inward rectifying potassium, sodium, leakage, and an electrogenic sodium pump) demonstrates the plausibility of the conceptual model. 11. These data suggest that a novel Na(+)-based mechanism for membrane potential oscillation is revealed by blockade of Ca2+ channels in leech ganglia.

scholarly journals Mechanisms of generation of membrane potential resonance in a neuron with multiple resonant ionic currents

2017 ◽  
Author(s):  
David M. Fox ◽  
Hua-an Tseng ◽  
Tomasz G. Smolinski ◽  
Horacio G. Rotstein ◽  
Farzan Nadim
Keyword(s):  
Membrane Potential ◽  
Resonant Frequency ◽  
Ionic Currents ◽  
Calcium Currents ◽  
Neuronal Membrane ◽  
Model Parameters ◽  
Time Constants ◽  
Voltage Range ◽  
Voltage Gated ◽  
Pyloric Network

AbstractNeuronal membrane potential resonance (MPR) is associated with subthreshold and network oscillations. A number of voltage-gated ionic currents can contribute to the generation or amplification of MPR, but how the interaction of these currents with linear currents contributes to MPR is not well understood. We explored this in the pacemaker PD neurons of the crab pyloric network. The PD neuron MPR is sensitive to blockers of H- (IH) and calcium-currents (ICa). We used the impedance profile of the biological PD neuron, measured in voltage clamp, to constrain parameter values of a conductance-based model using a genetic algorithm and obtained many optimal parameter combinations. Unlike most cases of MPR, in these optimal models, the values of resonant- (fres) and phasonant- (fφ=0) frequencies were almost identical. Taking advantage of this fact, we linked the peak phase of ionic currents to their amplitude, in order to provide a mechanistic explanation the dependence of MPR on the ICa gating variable time constants. Additionally, we found that distinct pairwise correlations between ICa parameters contributed to the maintenance of fres and resonance power (QZ). Measurements of the PD neuron MPR at more hyperpolarized voltages resulted in a reduction of fres but no change in QZ. Constraining the optimal models using these data unmasked a positive correlation between the maximal conductances of IH and ICa. Thus, although IH is not necessary for MPR in this neuron type, it contributes indirectly by constraining the parameters of ICa.Author SummaryMany neuron types exhibit membrane potential resonance (MPR) in which the neuron produces the largest response to oscillatory input at some preferred (resonant) frequency and, in many systems, the network frequency is correlated with neuronal MPR. MPR is captured by a peak in the impedance vs. frequency curve (Z-profile), which is shaped by the dynamics of voltage-gated ionic currents. Although neuron types can express variable levels of ionic currents, they may have a stable resonant frequency. We used the PD neuron of the crab pyloric network to understand how MPR emerges from the interplay of the biophysical properties of multiple ionic currents, each capable of generating resonance. We show the contribution of an inactivating current at the resonant frequency in terms of interacting time constants. We measured the Z-profile of the PD neuron and explored possible combinations of model parameters that fit this experimentally measured profile. We found that the Z-profile constrains and defines correlations among parameters associated with ionic currents. Furthermore, the resonant frequency and amplitude are sensitive to different parameter sets and can be preserved by co-varying pairs of parameters along their correlation lines. Furthermore, although a resonant current may be present in a neuron, it may not directly contribute to MPR, but constrain the properties of other currents that generate MPR. Finally, constraining model parameters further to those that modify their MPR properties to changes in voltage range produces maximal conductance correlations.

Characterization of Voltage-Gated K+ Currents Contributing to Subthreshold Membrane Potential Oscillations in Hippocampal CA1 Interneurons

2010 ◽  
Vol 103 (6) ◽  
pp. 3472-3489 ◽  
Author(s):  
France Morin ◽  
Darrell Haufler ◽  
Frances K. Skinner ◽  
Jean-Claude Lacaille
Keyword(s):  
Membrane Potential ◽  
Sodium Current ◽  
Rhythmic Activity ◽  
Delayed Rectifier ◽  
Inhibitory Interneurons ◽  
Potential Oscillations ◽  
Voltage Range ◽  
Voltage Gated ◽  
Delayed Rectifier Current ◽  
Membrane Potential Oscillations

CA1 inhibitory interneurons at the stratum lacunosum-moleculare and radiatum junction (LM/RAD-INs) display subthreshold membrane potential oscillations (MPOs) involving voltage-dependent Na+ and A-type K+ currents. LM/RAD-INs also express other voltage-gated K+ currents, although their properties and role in MPOs remain unclear. Here, we characterized these voltage-gated K+ currents and investigated their role in MPOs. Using outside-out patch recordings from LM/RAD-IN somata, we distinguished four voltage-gated K+ currents based on their pharmacology and activation/inactivation properties: a fast delayed rectifier current ( IKfast), a slow delayed rectifier current ( IKslow), a rapidly inactivating A-type current ( IA), and a slowly inactivating current ( ID). Their relative contribution to the total K+ current was IA > IKfast > IKslow = ID. The presence of ID and the relative contributions of K+ currents in LM/RAD-INs are different from those of other CA1 interneurons, suggesting the presence of differential complement of K+ currents in subgroups of interneurons. We next determined whether these K+ currents were sufficient for MPO generation using a single-compartment model of LM/RAD-INs. The model captured the subthreshold voltage dependence of MPOs. Moreover, all K+ currents were active at subthreshold potentials but ID, IA, and the persistent sodium current ( INaP) were most active near threshold. Using impedance analysis, we found that IA and INaP contribute to MPO generation by modulating peak spectral frequency during MPOs and governing the voltage range over which MPOs occur. Our findings uncover a differential expression of a complement of K+ channels that underlies intrinsic rhythmic activity in inhibitory interneurons.

Coupled Oscillator Model of the Dopaminergic Neuron of the Substantia Nigra

2000 ◽  
Vol 83 (5) ◽  
pp. 3084-3100 ◽  
Author(s):  
C. J. Wilson ◽  
J. C. Callaway
Keyword(s):  
Membrane Potential ◽  
Calcium Imaging ◽  
Dopaminergic Neurons ◽  
Calcium Current ◽  
Dopaminergic Neuron ◽  
Potassium Current ◽  
Potential Oscillation ◽  
Calcium Dependent ◽  
Membrane Potential Oscillation ◽  
Low Threshold

Calcium imaging using fura-2 and whole cell recording revealed the effective location of the oscillator mechanism on dopaminergic neurons of the substantia nigra, pars compacta, in slices from rats aged 15–20 days. As previously reported, dopaminergic neurons fired in a slow rhythmic single spiking pattern. The underlying membrane potential oscillation survived blockade of sodium currents with TTX and was enhanced by blockade of voltage-sensitive potassium currents with TEA. Calcium levels increased during the subthreshold depolarizing phase of the membrane potential oscillation and peaked at the onset of the hyperpolarizing phase as expected if the pacemaker potential were due to a low-threshold calcium current and the hyperpolarizing phase to calcium-dependent potassium current. Calcium oscillations were synchronous in the dendrites and soma and were greater in the dendrites than in the soma. Average calcium levels in the dendrites overshot steady-state levels and decayed over the course of seconds after the oscillation was resumed after having been halted by hyperpolarizing currents. Average calcium levels in the soma increased slowly, taking many cycles to achieve steady state. Voltage clamp with calcium imaging revealed the voltage dependence of the somatic calcium current without the artifacts of incomplete spatial voltage control. This showed that the calcium current had little or no inactivation and was half-maximal at −40 to −30 mV. The time constant of calcium removal was measured by the return of calcium to resting levels and depended on diameter. The calcium sensitivity of the calcium-dependent potassium current was estimated by plotting the slow tail current against calcium concentration during the decay of calcium to resting levels at −60 mV. A single compartment model of the dopaminergic neuron consisting of a noninactivating low-threshold calcium current, a calcium-dependent potassium current, and a small leak current reproduced most features of the membrane potential oscillations. The same currents much more accurately reproduced the calcium transients when distributed uniformly along a tapering cable in a multicompartment model. This model represented the dopaminergic neuron as a set of electrically coupled oscillators with different natural frequencies. Each frequency was determined by the surface area to volume ratio of the compartment. This model could account for additional features of the dopaminergic neurons seen in slices, such as slow adaptation of oscillation frequency and may produce irregular firing under different coupling conditions.

Interactive Effects of the GABABergic Modulation of Calcium Channels and Calcium-Dependent Potassium Channels in Lamprey

1999 ◽  
Vol 81 (3) ◽  
pp. 1318-1329 ◽  
Author(s):  
Jesper Tegnér ◽  
Sten Grillner
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Calcium Channels ◽  
Receptor Activation ◽  
Neuronal Firing ◽  
Calcium Currents ◽  
Interactive Effects ◽  
Potential Oscillations ◽  
Calcium Dependent ◽  
Membrane Potential Oscillations

Interactive effects of the GABABergic modulation of calcium channels and calcium-dependent potassium channels in lamprey. The GABAB-mediated modulation of spinal neurons in the lamprey is investigated in this study. Activation of GABAB receptors reduces calcium currents through both low- (LVA) and high-voltage activated (HVA) calcium channels, which subsequently results in the reduction of the calcium-dependent potassium (KCa) current. This in turn will reduce the peak amplitude of the afterhyperpolarization (AHP). We used the modulatory effects of GABAB receptor activation on N-methyl-d-aspartate (NMDA)-induced, TTX-resistant membrane potential oscillations as an experimental model in which to separate the effects of GABAB receptor activation on LVA calcium channels from that on KCachannels. We show experimentally and by using simulations that a direct effect on LVA calcium channels can account for the effects of GABAB receptor activation on intrinsic membrane potential oscillations to a larger extent than indirect effects mediated via KCa channels. Furthermore, by conducting experiments and simulations on intrinsic membrane potential oscillations, we find that KCa channels may be activated by calcium entering through LVA calcium channels, providing that the decay kinetics of the calcium that enters through LVA calcium channels is not as slow as the calcium entering via NMDA receptors. A combined experimental and computational analysis revealed that the LVA calcium current also contributes to neuronal firing properties.

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