scholarly journals Inward rectifier potassium current IKir promotes intrinsic pacemaker activity of thalamocortical neurons

2018 ◽  
Vol 119 (6) ◽  
pp. 2358-2372 ◽  
Author(s):  
Yimy Amarillo ◽  
Angela I. Tissone ◽  
Germán Mato ◽  
Marcela S. Nadal
Keyword(s):  
Membrane Potential ◽  
Bifurcation Analysis ◽  
Calcium Current ◽  
Potassium Current ◽  
Inward Rectifier ◽  
Burst Firing ◽  
Pacemaker Activity ◽  
Frequency Bands ◽  
Cationic Current ◽  
Low Threshold

Slow repetitive burst firing by hyperpolarized thalamocortical (TC) neurons correlates with global slow rhythms (<4 Hz), which are the physiological oscillations during non-rapid eye movement sleep or pathological oscillations during idiopathic epilepsy. The pacemaker activity of TC neurons depends on the expression of several subthreshold conductances, which are modulated in a behaviorally dependent manner. Here we show that upregulation of the small and neglected inward rectifier potassium current IKir induces repetitive burst firing at slow and delta frequency bands. We demonstrate this in mouse TC neurons in brain slices by manipulating the Kir maximum conductance with dynamic clamp. We also performed a thorough theoretical analysis that explains how the unique properties of IKir enable this current to induce slow periodic bursting in TC neurons. We describe a new ionic mechanism based on the voltage- and time-dependent interaction of IKir and hyperpolarization-activated cationic current Ih that endows TC neurons with the ability to oscillate spontaneously at very low frequencies, even below 0.5 Hz. Bifurcation analysis of conductance-based models of increasing complexity demonstrates that IKir induces bistability of the membrane potential at the same time that it induces sustained oscillations in combination with Ih and increases the robustness of low threshold-activated calcium current IT-mediated oscillations. NEW & NOTEWORTHY The strong inwardly rectifying potassium current IKir of thalamocortical neurons displays a region of negative slope conductance in the current-voltage relationship that generates potassium currents activated by hyperpolarization. Bifurcation analysis shows that IKir induces bistability of the membrane potential; generates sustained subthreshold oscillations by interacting with the hyperpolarization-activated cationic current Ih; and increases the robustness of oscillations mediated by the low threshold-activated calcium current IT. Upregulation of IKir in thalamocortical neurons induces repetitive burst firing at slow and delta frequency bands (<4 Hz).

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.

scholarly journals The interplay of seven subthreshold conductances controls the resting membrane potential and the oscillatory behavior of thalamocortical neurons

2014 ◽  
Vol 112 (2) ◽  
pp. 393-410 ◽  
Author(s):  
Yimy Amarillo ◽  
Edward Zagha ◽  
German Mato ◽  
Bernardo Rudy ◽  
Marcela S. Nadal
Keyword(s):  
Steady State ◽  
Membrane Potential ◽  
Computational Model ◽  
Potassium Current ◽  
Brain Slices ◽  
Reversal Potential ◽  
Burst Firing ◽  
Resting Membrane Potential ◽  
Cationic Current ◽  
Steady State Current

The signaling properties of thalamocortical (TC) neurons depend on the diversity of ion conductance mechanisms that underlie their rich membrane behavior at subthreshold potentials. Using patch-clamp recordings of TC neurons in brain slices from mice and a realistic conductance-based computational model, we characterized seven subthreshold ion currents of TC neurons and quantified their individual contributions to the total steady-state conductance at levels below tonic firing threshold. We then used the TC neuron model to show that the resting membrane potential results from the interplay of several inward and outward currents over a background provided by the potassium and sodium leak currents. The steady-state conductances of depolarizing Ih (hyperpolarization-activated cationic current), IT (low-threshold calcium current), and INaP (persistent sodium current) move the membrane potential away from the reversal potential of the leak conductances. This depolarization is counteracted in turn by the hyperpolarizing steady-state current of IA (fast transient A-type potassium current) and IKir (inwardly rectifying potassium current). Using the computational model, we have shown that single parameter variations compatible with physiological or pathological modulation promote burst firing periodicity. The balance between three amplifying variables (activation of IT, activation of INaP, and activation of IKir) and three recovering variables (inactivation of IT, activation of IA, and activation of Ih) determines the propensity, or lack thereof, of repetitive burst firing of TC neurons. We also have determined the specific roles that each of these variables have during the intrinsic oscillation.

Modulation of a subthreshold calcium current by the neuropeptide FMRFamide in Aplysia neuron R15

1988 ◽  
Vol 60 (5) ◽  
pp. 1728-1738 ◽  
Author(s):  
R. H. Kramer ◽  
E. S. Levitan ◽  
G. M. Carrow ◽  
I. B. Levitan
Keyword(s):  
Membrane Potential ◽  
Cyclic Amp ◽  
Calcium Channels ◽  
Calcium Current ◽  
Molecular Mechanisms ◽  
Chloride Ions ◽  
Egg Laying ◽  
Pacemaker Activity ◽  
Channel Blockers ◽  
Inward Current

1. The effect of the endogenous neuropeptide FMRFamide (Phe-Met-Arg-Phe-amide) on the Aplysia bursting pacemaker neuron R15 was studied. Brief local applications of FMRFamide, both on R15 somata in situ, and on R15 somata that were isolated and maintained in primary cell culture, cause a hyperpolarization of the membrane potential and a suppression of spontaneous bursting or beating pacemaker activity. 2. Two-electrode voltage-clamp experiments revealed that FMRFamide decreases the amplitude of an inward current, which activates with depolarization starting at a membrane potential less depolarized than the threshold for action potentials. Previous studies have established that this subthreshold inward current is carried by calcium and is essential for the generation of bursting pacemaker activity in Aplysia neurons. The effect of FMRFamide on the subthreshold inward current of R15 is blocked by divalent cation calcium channel blockers, such as cobalt and manganese, and is unaffected by changing the external concentration of potassium or chloride ions, or addition of blockers of the calcium-activated potassium current, such as external tetraethylammonium or internal EGTA. 3. The subthreshold calcium current of R15 is also decreased by dopamine and by an unidentified synaptic neurotransmitter. These substances mimic and occlude the action of FMRFamide on the subthreshold calcium current, suggesting that all three transmitters converge to affect the same population of calcium channels in neuron R15. 4. The subthreshold calcium current is enhanced by neurotransmitters that elevate cyclic AMP in R15, including serotonin, and the Aplysia neuropeptide egg-laying hormone (ELH). Likewise, the effect of FMRFamide on the subthreshold calcium current is enhanced by serotonin, ELH, and a cyclic AMP analog, suggesting that FMRFamide and cyclic AMP have antagonistic actions on the same population of calcium channels in neuron R15. 5. We conclude that the suppression of spontaneous bursting or beating pacemaker activity in neuron R15 by FMRFamide is due to a decrease in the subthreshold calcium current. The subthreshold calcium current in R15 is a common target for modulation by many different transmitters, acting via several distinct molecular mechanisms.

Membrane currents of retinal bipolar cells in culture

1988 ◽  
Vol 60 (4) ◽  
pp. 1460-1480 ◽  
Author(s):  
E. M. Lasater
Keyword(s):  
Cell Culture ◽  
Calcium Current ◽  
Potassium Current ◽  
Inward Rectifier ◽  
Bipolar Cells ◽  
Membrane Currents ◽  
Membrane Properties ◽  
White Bass ◽  
Retinal Bipolar Cells ◽  
A Current

1. Retinal bipolar cells were isolated from white bass retinas and maintained in a cell culture preparation. Two morphological types of bipolar cells were observed in cell culture. These were labeled large- and small-bipolar cells based mainly on the size of their somata and primary dendrites. Two types of small-bipolar cells were observed. Isolated bass bipolar cells are very similar to those described in the intact retina. 2. Under current clamp, to depolarizing current injection, small-bipolar cells produced a spike followed by a plateau. Large-bipolar cells showed a slow depolarization to a plateau level. 3. Voltage-gated membrane currents were studied using whole-cell patch-clamp techniques. Channel blocking agents were used to define the ion channels found in the membranes of these cells. 4. The large-bipolar cells were found to possess an A-current, a calcium current, and a calcium-dependent potassium current. 5. Large bipolar cells also possessed an inward rectifier that did not correspond to any previously described. 6. The two types of small-bipolar cells were found to have very similar membrane properties to one another. They lacked a large A-current but possessed a slowly activating, outward rectifying potassium current. Similar to the large-bipolar cells, they showed a calcium current and a calcium-activated potassium current. 7. The inward rectifier of small-bipolar cells was characterized as an H-current. 8. The results suggest that the membrane currents of bipolar cells set a narrow operating range about which the cells function in the intact retina. In addition these currents help shape the responses of bipolar cells to light stimuli but do not confer ON or OFF properties.

Synchronized Oscillations in the Inferior Olive Are Controlled by the Hyperpolarization-Activated Cation Current I h

1997 ◽  
Vol 77 (6) ◽  
pp. 3145-3156 ◽  
Author(s):  
Thierry Bal ◽  
David A. McCormick
Keyword(s):  
Membrane Potential ◽  
Guinea Pig ◽  
Inferior Olive ◽  
Local Application ◽  
Partial Replacement ◽  
Resting Membrane Potential ◽  
Pacemaker Potential ◽  
Cationic Current ◽  
Cation Current ◽  
Low Threshold

Bal, Thierry and David A. McCormick. Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I h. J. Neurophysiol. 77: 3145–3156, 1997. The participation of a hyperpolarization-activated cationic current in the generation of oscillations in single inferior olive neurons and in the generation of ensemble oscillations in the inferior olive nucleus (IO) of the guinea pig and ferret was investigated in slices maintained in vitro. Intracellular recordings in guinea pig or ferret IO neurons revealed that these cells could generate sustained endogenous oscillations (4–10 Hz) at hyperpolarized membrane potentials (−60 to −67 mV) after the intracellular injection of a brief hyperpolarizing current pulse. These oscillations appeared as the rhythmic generation of a low-threshold Ca2+ spike that typically initiated one or two fast Na+-dependent action potentials. Between low-threshold Ca2+ spikes was an afterhyperpolarization that formed a “pacemaker” potential. Local application of apamin resulted in a large reduction in the amplitude of the afterhyperpolarization, indicating that a Ca2+-activated K+ current makes a strong contribution to its generation. However, even in the presence of apamin, hyperpolarization of IO neurons results in a “depolarizing sag” of the membrane potential that was blocked by local application of Cs+ or partial replacement of extracellular Na+ with choline+ or N-methyl-d-glucamine+, suggesting that I h also contributes to the generation of the afterhyperpolarization. Extracellular application of low concentrations of cesium resulted in hyperpolarization of the membrane potential of IO neurons and spontaneous 5- to 6-Hz oscillations in single, as well as networks, of IO neurons. Application of larger concentrations of cesium reduced the frequency of oscillation to 2–3 Hz or blocked the oscillation entirely. On the basis of these results, we propose that I h contributes to single and ensemble oscillations in the IO in two ways: 1) I h contributes to the determination of the resting membrane potential such that reduction of I h results in hyperpolarization of the membrane potential and an increased propensity of oscillation through removal of inactivation of the low-threshold Ca2+ current; and 2) I h contributes to the generation of the afterhyperpolarization and the pacemaker potential between low-threshold Ca2+ spikes.

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