Research articleβ-Adrenergic receptor agonist increases voltage-gated Na+ currents in medial prefrontal cortex pyramidal neurons
Introduction
The prefrontal cortex does not function properly during acute and chronic stress; this dysfunction is associated with excessive noradrenaline release. PFC function is also impaired in neuropsychiatric disorders, for example, ADHD, depression and schizophrenia [9], [20].
β-Adrenergic receptors are G-protein coupled receptors that influence cellular effectors via second messengers [22], [18]. A β-adrenergic agonist has been reported to enhance the calcium currents in the amygdala and the Ih currents in the cerebellum [11], [22]. β-Adrenergic receptors in the PFC also influence working memory [19].
There are many reports showing that β-adrenergic receptor stimulation enhances excitatory synaptic transmission in the brain. Isoproterenol enhances the evoked excitatory postsynaptic currents in the medial PFC [12], [10]. Moreover, in hippocampal neurons, β-adrenergic receptors must be activated during certain patterns of synaptic stimulation to induce LTP [13]. Furthermore, in the amygdala and in the hippocampus, β-adrenergic receptor stimulation itself is sufficient to induce LTP [11].
The influence of neurotransmitters on fast voltage-gated Na+ channels has already been assessed in the whole-cell configuration. Serotonin receptor activation decreased the maximal amplitude of Na+ currents in the neurons of the PFC [4], and dopamine receptor stimulation inhibited the peak Na+ currents in the hippocampus [3].
The aim of this study was to elucidate the function of β-adrenergic receptors in regulating voltage-dependent and fast-inactivating Na+ currents in mPFC pyramidal neurons.
Section snippets
Preparation of slices
The experimental procedures used in this study adhered to the institutional and international guidelines on the ethical use of animals (II local ethical committee decision 1/2009). The experiments were performed on the neurons of 3-week-old male rats. Brain slices were prepared as previously described [24], [16]. After the induction of deep anesthesia using ethyl chloride, the brains were removed and placed in a cold (0–4 °C), sucrose-based solution [16], [24]. Coronal slices (300 μm thick) were
The effect of isoproterenol on the membrane potential
The treatment of pyramidal neurons with 2 μM isoproterenol depolarized the membrane potential of mPFC pyramidal neurons, as measured using perforated-patch recordings (Fig. 1Aa, −64.9 ± 5.2 mV in the control vs. −62.6 ± 5.3 mV during isoproterenol treatment, n = 5). The average membrane potential change exerted by isoproterenol was +2.3 ± 0.2 mV (n = 5, paired t-test, p = 0.0004, Fig. 1Ac left bar). Isoproterenol may cause this depolarization by opening Ih channels or closing leak potassium channels [22], [25]
Discussion
The recordings were performed from several sodium channels located in the patch membrane (macropatch). All sodium channels recordings were obtained in the presence of Cs+ ions to abolish the depolarization induced by isoproterenol (see results).
In entorhinal cortex neurons and in PFC pyramidal neurons (cell-attached recordings), dopamine receptor activation shifted the Na+ current activation curve toward hyperpolarization, exactly as shown in this study [24], [21]. Moreover, in ventricular
Acknowledgements
I would like to thank Marta Kuzniarska and Izabela Zaborowska for their technical assistance. This study was sponsored by grants Nos. NN401584638 and NN301572940.
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