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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

General properties. (A–C) Representative currents obtained in response to hyperpolarizing pulses in 32.5 mM external K+ solution: (A) EC1 saline with 1 mM kynurenic acid, 10 μM bicuculline (BL1 mix), 0.6 μM TTX, 100 μM Cd2+; (B) same solution as in A plus 10 μM ivabradine; (C) same solution as in B plus 2 mM Ba2+. Voltage steps from a holding potential of −40 mV with hyperpolarizing steps ranging from −60 to −130 mV in 10 mV increments. (D): I–V relationship of peak (green dots) and steady-state (blue dots) current; mean current amplitude of 81 cell recordings. Vertical error bars represent standard error; EC2 saline, with BL1 and BL2 mixes of blockers. (E) Instantaneous I/V curve during application of a 220 mV/s ramp protocol (from −180 to +40 mV, 0.23 V/s) in a DA PG cell perfused with the solution described in (A), after subtraction of the ohmic leak; the red dot (−41.3 mV) marks the observed reversal potential, the green dot the Nernstian equilibrium potential in the experimental conditions used ([K+]o = 32.5 mM). All the experiments shown in this figure were performed in slice, perforated patch configuration, at 34°C.
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Figure 1: General properties. (A–C) Representative currents obtained in response to hyperpolarizing pulses in 32.5 mM external K+ solution: (A) EC1 saline with 1 mM kynurenic acid, 10 μM bicuculline (BL1 mix), 0.6 μM TTX, 100 μM Cd2+; (B) same solution as in A plus 10 μM ivabradine; (C) same solution as in B plus 2 mM Ba2+. Voltage steps from a holding potential of −40 mV with hyperpolarizing steps ranging from −60 to −130 mV in 10 mV increments. (D): I–V relationship of peak (green dots) and steady-state (blue dots) current; mean current amplitude of 81 cell recordings. Vertical error bars represent standard error; EC2 saline, with BL1 and BL2 mixes of blockers. (E) Instantaneous I/V curve during application of a 220 mV/s ramp protocol (from −180 to +40 mV, 0.23 V/s) in a DA PG cell perfused with the solution described in (A), after subtraction of the ohmic leak; the red dot (−41.3 mV) marks the observed reversal potential, the green dot the Nernstian equilibrium potential in the experimental conditions used ([K+]o = 32.5 mM). All the experiments shown in this figure were performed in slice, perforated patch configuration, at 34°C.

Mentions: In a first series of experiments, carried out using perforated patch recordings in slice at 34°C, hyperpolarizing steps were delivered from a holding potential of −40 mV, which is close to the predicted K+ equilibrium potential in our experimental conditions (EK = −37.7 mV for [K+]o = 32.5 mM), to potentials ranging from −60 to −130 mV (10 mV increments, 10 s interval). The inward current obtained in response is shown in Figure 1A; a fraction of this current could be suppressed by two organic compounds known as selective HCN channels blockers, i.e., ZD7288 30 μM (BoSmith et al., 1993) and S-16257, a.k.a. ivabradine, 10 μM; (Bois et al., 1996; Bucchi et al., 2002), Figure 1B; the h-current in DA-PG cells has been the object of another study (Pignatelli et al., 2013), and will be not further discussed in this paper.


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)

General properties. (A–C) Representative currents obtained in response to hyperpolarizing pulses in 32.5 mM external K+ solution: (A) EC1 saline with 1 mM kynurenic acid, 10 μM bicuculline (BL1 mix), 0.6 μM TTX, 100 μM Cd2+; (B) same solution as in A plus 10 μM ivabradine; (C) same solution as in B plus 2 mM Ba2+. Voltage steps from a holding potential of −40 mV with hyperpolarizing steps ranging from −60 to −130 mV in 10 mV increments. (D): I–V relationship of peak (green dots) and steady-state (blue dots) current; mean current amplitude of 81 cell recordings. Vertical error bars represent standard error; EC2 saline, with BL1 and BL2 mixes of blockers. (E) Instantaneous I/V curve during application of a 220 mV/s ramp protocol (from −180 to +40 mV, 0.23 V/s) in a DA PG cell perfused with the solution described in (A), after subtraction of the ohmic leak; the red dot (−41.3 mV) marks the observed reversal potential, the green dot the Nernstian equilibrium potential in the experimental conditions used ([K+]o = 32.5 mM). All the experiments shown in this figure were performed in slice, perforated patch configuration, at 34°C.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: General properties. (A–C) Representative currents obtained in response to hyperpolarizing pulses in 32.5 mM external K+ solution: (A) EC1 saline with 1 mM kynurenic acid, 10 μM bicuculline (BL1 mix), 0.6 μM TTX, 100 μM Cd2+; (B) same solution as in A plus 10 μM ivabradine; (C) same solution as in B plus 2 mM Ba2+. Voltage steps from a holding potential of −40 mV with hyperpolarizing steps ranging from −60 to −130 mV in 10 mV increments. (D): I–V relationship of peak (green dots) and steady-state (blue dots) current; mean current amplitude of 81 cell recordings. Vertical error bars represent standard error; EC2 saline, with BL1 and BL2 mixes of blockers. (E) Instantaneous I/V curve during application of a 220 mV/s ramp protocol (from −180 to +40 mV, 0.23 V/s) in a DA PG cell perfused with the solution described in (A), after subtraction of the ohmic leak; the red dot (−41.3 mV) marks the observed reversal potential, the green dot the Nernstian equilibrium potential in the experimental conditions used ([K+]o = 32.5 mM). All the experiments shown in this figure were performed in slice, perforated patch configuration, at 34°C.
Mentions: In a first series of experiments, carried out using perforated patch recordings in slice at 34°C, hyperpolarizing steps were delivered from a holding potential of −40 mV, which is close to the predicted K+ equilibrium potential in our experimental conditions (EK = −37.7 mV for [K+]o = 32.5 mM), to potentials ranging from −60 to −130 mV (10 mV increments, 10 s interval). The inward current obtained in response is shown in Figure 1A; a fraction of this current could be suppressed by two organic compounds known as selective HCN channels blockers, i.e., ZD7288 30 μM (BoSmith et al., 1993) and S-16257, a.k.a. ivabradine, 10 μM; (Bois et al., 1996; Bucchi et al., 2002), Figure 1B; the h-current in DA-PG cells has been the object of another study (Pignatelli et al., 2013), and will be not further discussed in this paper.

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