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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

Modulation of IKir by cAMP. (A–C) Effect of forskolin. Current tracings in control (A) and in the presence of 10 μM forskolin plus 100 μM IBMX (B); (C) comparison of the I/V curves recorded in control (blue dots) and forskolin (green dots); n = 12; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. (D–F) Effect of 8Br-cAMP. Current tracings in control (D) and in the presence of 10 μM 8Br-cAMP (E); (F) Comparison of the I/V curves recorded in control (blue dots) and 8Br-cAMP (green dots); n = 6; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. All recordings were realized in EC2 with the addition of BL1 and BL2, at 34°C.
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Figure 8: Modulation of IKir by cAMP. (A–C) Effect of forskolin. Current tracings in control (A) and in the presence of 10 μM forskolin plus 100 μM IBMX (B); (C) comparison of the I/V curves recorded in control (blue dots) and forskolin (green dots); n = 12; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. (D–F) Effect of 8Br-cAMP. Current tracings in control (D) and in the presence of 10 μM 8Br-cAMP (E); (F) Comparison of the I/V curves recorded in control (blue dots) and 8Br-cAMP (green dots); n = 6; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. All recordings were realized in EC2 with the addition of BL1 and BL2, at 34°C.

Mentions: Under voltage-clamp conditions, the addition to the extracellular solution of 10 μM forskolin, a classical activator of adenylyl cyclase (Seamon and Daly, 1981) and 0.1 mM IBMX, a phosphodiesterase inhibitor, induces a decrease of the Kir current (Figures 8A–C): the stimulation of the cAMP synthesis reduces the IKir amplitude of 12.3 ± 0.22 % in the range from −80 to −130 mV (n = 12; p < 0.01).


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)

Modulation of IKir by cAMP. (A–C) Effect of forskolin. Current tracings in control (A) and in the presence of 10 μM forskolin plus 100 μM IBMX (B); (C) comparison of the I/V curves recorded in control (blue dots) and forskolin (green dots); n = 12; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. (D–F) Effect of 8Br-cAMP. Current tracings in control (D) and in the presence of 10 μM 8Br-cAMP (E); (F) Comparison of the I/V curves recorded in control (blue dots) and 8Br-cAMP (green dots); n = 6; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. All recordings were realized in EC2 with the addition of BL1 and BL2, at 34°C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 8: Modulation of IKir by cAMP. (A–C) Effect of forskolin. Current tracings in control (A) and in the presence of 10 μM forskolin plus 100 μM IBMX (B); (C) comparison of the I/V curves recorded in control (blue dots) and forskolin (green dots); n = 12; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. (D–F) Effect of 8Br-cAMP. Current tracings in control (D) and in the presence of 10 μM 8Br-cAMP (E); (F) Comparison of the I/V curves recorded in control (blue dots) and 8Br-cAMP (green dots); n = 6; the difference, tested with Two-Way ANOVA and post-hoc Bonferroni test, is significant for the potentials more negative than −80 mV. All recordings were realized in EC2 with the addition of BL1 and BL2, at 34°C.
Mentions: Under voltage-clamp conditions, the addition to the extracellular solution of 10 μM forskolin, a classical activator of adenylyl cyclase (Seamon and Daly, 1981) and 0.1 mM IBMX, a phosphodiesterase inhibitor, induces a decrease of the Kir current (Figures 8A–C): the stimulation of the cAMP synthesis reduces the IKir amplitude of 12.3 ± 0.22 % in the range from −80 to −130 mV (n = 12; p < 0.01).

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