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 (Ih) by showing full activation in <10 ms, no inactivation, suppression by Ba2+ in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba2+ (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.
Highlights
The background potassium conductance mediated by inward rectifying potassium channels impacts on many physiological processes, from the excitability profile of nerve and muscle cells to hormone release
We restricted the analysis to PG cells; these were selected on the basis of their location around the glomerular border, dendritic arborization extending within the glomerular neuropil, membrane capacitance (8.0 ± 0.2 pF; n = 297) and input resistance (979.4 ± 33.4 M ; n = 276)
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
Summary
The background potassium conductance mediated by inward rectifying potassium channels impacts on many physiological processes, from the excitability profile of nerve and muscle cells to hormone release. Dopaminergic (DA) neurons represent an estimated 10–16% of the neurons residing in the most external (glomerular) layer of the main olfactory bulb (MOB) (Halász et al, 1977; McLean and Shipley, 1988). Analyzing the excitability profile of DA-PG cells, we observed that Ba2+ (300 μM, a blocker of the Kir channels), induced a large depolarization in bulbar DA neurons, large enough to lead to complete blockage of spontaneous firing of these cells. The current can be better evidenced with ionic manipulations causing a depolarizing shift of the potassium equilibrium potential, but even under physiological conditions, for the elevated input resistance of these cells, the Kir current is sufficiently large to exert a relevant influence on the cell excitability profile
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