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Inward rectifier potassium (Kir) current in dopaminergic periglomerular neurons of the mouse olfactory bulb.

Borin M, Fogli Iseppe A, Pignatelli A, Belluzzi O - Front Cell Neurosci (2014)

Bottom Line: The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP.We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors.These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Biotechnology, University of Ferrara Ferrara, Italy.

ABSTRACT
Dopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are autorhythmic and are the target of numerous terminals releasing a variety of neurotransmitters. Despite the centrality of their position, suggesting a critical role in the sensory processing, their properties -and consequently their function- remain elusive. The current mediated by inward rectifier potassium (Kir) channels in DA-PG cells was recorded by adopting the perforated-patch configuration in thin slices; IKir could be distinguished from the hyperpolarization-activated current (I h ) by showing full activation in <10 ms, no inactivation, suppression by Ba(2+) in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba(2+) (2 mM) induces a large depolarization of DA-PG cells, paralleled by an increase of the input resistance, leading to a block of the spontaneous activity, but the Kir current is not an essential component of the pacemaker machinery. The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP. We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors. These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility.

No MeSH data available.


Related in: MedlinePlus

Potassium sensitivity. (A) Effect of changing [K+]o on membrane current. Average currents (n = 8) at the indicated external potassium concentrations in response to voltage ramps from −170 to +20 mV from a holding potential of −40 mV, 0.22 V/s; perforated patches; the bathing solution included Bl1 and Bl2. (B) Box charts showing the reversal potentials at different [K+]o [same color code as in (A)]; black arrow heads to the right of each box mark the expected reversal potentials predicted by the Nernst equation. In the box charts, here and in the following, the square in the center of the box represents the mean value, the horizontal line crossing the box indicates the median, the range of the box represents standard error and the whiskers define the 10–90% range of data sample. (C) Plot of the reversal potential for the inwardly rectifying current against the logarithm of [K+]o. The linear regression fit (black dash line) has a slope of −61.9 mV, close to the theoretical value of −61 mV predicted by the Nernst equation (red line). (D) K+- and voltage-dependence of chord conductance (gKir); the chord conductance was calculated using the equation gKir = IKir/(Vm − EK), where IKir = steady state current. gKir plotted as a function of voltage-clamp test potentials at 2.5, 10, and 32.5 mM [K+]o. (E) Data in (D) replotted as a function of the driving force. Data points were fitted by Boltzmann curve using a least-squares method; n for 2.5, 10, and 32.5 mM was 7, 5, and 12, respectively.
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Figure 3: Potassium sensitivity. (A) Effect of changing [K+]o on membrane current. Average currents (n = 8) at the indicated external potassium concentrations in response to voltage ramps from −170 to +20 mV from a holding potential of −40 mV, 0.22 V/s; perforated patches; the bathing solution included Bl1 and Bl2. (B) Box charts showing the reversal potentials at different [K+]o [same color code as in (A)]; black arrow heads to the right of each box mark the expected reversal potentials predicted by the Nernst equation. In the box charts, here and in the following, the square in the center of the box represents the mean value, the horizontal line crossing the box indicates the median, the range of the box represents standard error and the whiskers define the 10–90% range of data sample. (C) Plot of the reversal potential for the inwardly rectifying current against the logarithm of [K+]o. The linear regression fit (black dash line) has a slope of −61.9 mV, close to the theoretical value of −61 mV predicted by the Nernst equation (red line). (D) K+- and voltage-dependence of chord conductance (gKir); the chord conductance was calculated using the equation gKir = IKir/(Vm − EK), where IKir = steady state current. gKir plotted as a function of voltage-clamp test potentials at 2.5, 10, and 32.5 mM [K+]o. (E) Data in (D) replotted as a function of the driving force. Data points were fitted by Boltzmann curve using a least-squares method; n for 2.5, 10, and 32.5 mM was 7, 5, and 12, respectively.

Mentions: The Kir channels are selective for K+ ions, and consequently the reversal potentials of the inward rectifying current for different extracellular K+ concentrations should always follow the Nernstian equilibrium potential for potassium (Figures 1E, 3A). When the [K+]o was changed from 2.5 to 10 and 32.5 mM, the reversal potentials progressively shifted toward more positive potentials (−105.12 ± 3.67 mV, n = 15, for 2.5 mM; −56.67 ± 9.78 mV, n = 9, for 10 mM; −36.78 mV ± 1.89, n = 27, for 32.5 mM); the reversal potentials in the different experimental conditions are represented in Figure 3B, where they are compared to the theoretical Nernstian equilibrium potentials for K+ ions (black triangles). The plot of the reversal potentials against the logarithm of [K+]o gives a linear relationship (r2 = 0.93) with a slope of −61.9 mV, close to the theoretical value of −61.0 mV predicted by the Nernst equation (Figure 3C).


Inward rectifier potassium (Kir) current in dopaminergic periglomerular neurons of the mouse olfactory bulb.

Borin M, Fogli Iseppe A, Pignatelli A, Belluzzi O - Front Cell Neurosci (2014)

Potassium sensitivity. (A) Effect of changing [K+]o on membrane current. Average currents (n = 8) at the indicated external potassium concentrations in response to voltage ramps from −170 to +20 mV from a holding potential of −40 mV, 0.22 V/s; perforated patches; the bathing solution included Bl1 and Bl2. (B) Box charts showing the reversal potentials at different [K+]o [same color code as in (A)]; black arrow heads to the right of each box mark the expected reversal potentials predicted by the Nernst equation. In the box charts, here and in the following, the square in the center of the box represents the mean value, the horizontal line crossing the box indicates the median, the range of the box represents standard error and the whiskers define the 10–90% range of data sample. (C) Plot of the reversal potential for the inwardly rectifying current against the logarithm of [K+]o. The linear regression fit (black dash line) has a slope of −61.9 mV, close to the theoretical value of −61 mV predicted by the Nernst equation (red line). (D) K+- and voltage-dependence of chord conductance (gKir); the chord conductance was calculated using the equation gKir = IKir/(Vm − EK), where IKir = steady state current. gKir plotted as a function of voltage-clamp test potentials at 2.5, 10, and 32.5 mM [K+]o. (E) Data in (D) replotted as a function of the driving force. Data points were fitted by Boltzmann curve using a least-squares method; n for 2.5, 10, and 32.5 mM was 7, 5, and 12, respectively.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4126183&req=5

Figure 3: Potassium sensitivity. (A) Effect of changing [K+]o on membrane current. Average currents (n = 8) at the indicated external potassium concentrations in response to voltage ramps from −170 to +20 mV from a holding potential of −40 mV, 0.22 V/s; perforated patches; the bathing solution included Bl1 and Bl2. (B) Box charts showing the reversal potentials at different [K+]o [same color code as in (A)]; black arrow heads to the right of each box mark the expected reversal potentials predicted by the Nernst equation. In the box charts, here and in the following, the square in the center of the box represents the mean value, the horizontal line crossing the box indicates the median, the range of the box represents standard error and the whiskers define the 10–90% range of data sample. (C) Plot of the reversal potential for the inwardly rectifying current against the logarithm of [K+]o. The linear regression fit (black dash line) has a slope of −61.9 mV, close to the theoretical value of −61 mV predicted by the Nernst equation (red line). (D) K+- and voltage-dependence of chord conductance (gKir); the chord conductance was calculated using the equation gKir = IKir/(Vm − EK), where IKir = steady state current. gKir plotted as a function of voltage-clamp test potentials at 2.5, 10, and 32.5 mM [K+]o. (E) Data in (D) replotted as a function of the driving force. Data points were fitted by Boltzmann curve using a least-squares method; n for 2.5, 10, and 32.5 mM was 7, 5, and 12, respectively.
Mentions: The Kir channels are selective for K+ ions, and consequently the reversal potentials of the inward rectifying current for different extracellular K+ concentrations should always follow the Nernstian equilibrium potential for potassium (Figures 1E, 3A). When the [K+]o was changed from 2.5 to 10 and 32.5 mM, the reversal potentials progressively shifted toward more positive potentials (−105.12 ± 3.67 mV, n = 15, for 2.5 mM; −56.67 ± 9.78 mV, n = 9, for 10 mM; −36.78 mV ± 1.89, n = 27, for 32.5 mM); the reversal potentials in the different experimental conditions are represented in Figure 3B, where they are compared to the theoretical Nernstian equilibrium potentials for K+ ions (black triangles). The plot of the reversal potentials against the logarithm of [K+]o gives a linear relationship (r2 = 0.93) with a slope of −61.9 mV, close to the theoretical value of −61.0 mV predicted by the Nernst equation (Figure 3C).

Bottom Line: The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP.We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors.These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Sciences and Biotechnology, University of Ferrara Ferrara, Italy.

ABSTRACT
Dopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are autorhythmic and are the target of numerous terminals releasing a variety of neurotransmitters. Despite the centrality of their position, suggesting a critical role in the sensory processing, their properties -and consequently their function- remain elusive. The current mediated by inward rectifier potassium (Kir) channels in DA-PG cells was recorded by adopting the perforated-patch configuration in thin slices; IKir could be distinguished from the hyperpolarization-activated current (I h ) by showing full activation in <10 ms, no inactivation, suppression by Ba(2+) in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba(2+) (2 mM) induces a large depolarization of DA-PG cells, paralleled by an increase of the input resistance, leading to a block of the spontaneous activity, but the Kir current is not an essential component of the pacemaker machinery. The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP. We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors. These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility.

No MeSH data available.


Related in: MedlinePlus