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It has been repeatedly proved that Nav1.8 tetrodotoxin (TTX)‐resistant sodium currents are expressed in peripheral sensory neurons where they play important role in nociception. There are very few publications that show the presence of TTX‐resistant sodium currents in central neurons. The aim of this study was to assess if functional Nav1.8 TTX‐resistant sodium currents are expressed in prefrontal cortex pyramidal neurons. All recordings were performed in the presence of TTX in the extracellular solution to block TTX‐sensitive sodium currents. The TTX‐resistant sodium current recorded in this study was mainly carried by the Nav1.8 sodium channel isoform because the Nav1.9 current was inhibited by the −65 mV holding potential that we used throughout the study. Moreover, the sodium current that we recorded was inhibited by treatment with the selective Nav1.8 inhibitor A‐803467. Confocal microscopy experiments confirmed the presence of the Nav1.8 α subunit in prefrontal cortex pyramidal neurons. Activation and steady state inactivation properties of TTX‐resistant sodium currents were also assessed in this study and they were similar to activation and inactivation properties of TTX‐resistant sodium currents expressed in dorsal root ganglia (DRG) neurons. Moreover, this study showed that carbamazepine (60 µM) inhibited the maximal amplitude of the TTX‐resistant sodium current. Furthermore, we found that carbamazepine shifts steady state inactivation curve of TTX‐resistant sodium currents toward hyperpolarization. This study suggests that the Nav1.8 TTX‐resistant sodium channel is expressed not only in DRG neurons, but also in cortical neurons and may be molecular target for antiepileptic drugs such as carbamazepine. [ABSTRACT FROM AUTHOR]

[Display omitted] • TRPM8 agonist menthol is a natural compound which evokes cold sensations by activating peripheral neurons. • Little is known about its effects on brain neurons. • We show that menthol inhibits Na + channels and exerts potent antiepileptic effects in PFC pyramidal neurons in vitro. • Antiepileptic effects of menthol are independent on TRPM8 channels. • Menthol and carbamazepine inhibit epileptic events to a similar extent. Menthol is a natural compound that evokes cold sensations by activating TRPM8 channels in peripheral sensory receptors. Little is known about the effects of this compound on brain neurons. It has been shown previously that menthol exerts antiepileptic effects in hippocampal neurons by enhancing GABA receptors. The aim of this patch-clamp study was to assess the effects of menthol on sodium currents, action potentials and epileptiform events in cortical neurons. Menthol inhibited fast voltage-gated sodium channels and neuronal excitability defined as the number of action potentials per depolarization step. The influence of menthol on epileptic events was also assessed in this study. Interictal epileptiform events lasting <2 s were recorded in zero magnesium high potassium proepileptic extracellular solution. The frequency of these epileptiform events was inhibited by menthol (200 µM). Ictal epileptic events lasting >100 s were recorded in zero magnesium proepileptic extracellular solution containing 4-AP. The frequency of these ictal events was potently decreased by menthol. TRPM8 channels were not involved in the inhibitory effect of menthol on ictal events because epileptic discharges persisted in the presence of the TRPM8 inhibitor AMTB. Moreover, ictal events were inhibited by therapeutic concentrations of the antiepileptic drug carbamazepine. Menthol and carbamazepine inhibited ictal events to a similar extent. This study showed that menthol exerts antiepileptic effects in cortical neurons. [ABSTRACT FROM AUTHOR]

Abstract: This study assesses the effects of ATP and GTP on the kinetic properties of voltage-gated K+ currents in anatomically identified postganglionic sympathetic neurons innervating the submandibular gland and the masseter muscle in rats. Three types of K+ currents were isolated: the I Af steady-state inactivating at more hyperpolarized potentials, I As steady-state inactivating at less hyperpolarized potentials than I Af and the I K current independent of membrane potential. The kinetic properties of these currents were tested in neurons with ATP (4 mM) and GTP (0.5 mM) or without ATP and GTP in the intracellular solution.In glandular and muscular neurons in the absence of ATP and GTP in the intracellular solution, the current density of I Af was significantly larger (142 pA/pF and 166 pA/pF, respectively) comparing to cells with ATP and GTP (96 pA/pF and 100 pA/pF, respectively). The I As was larger only in glandular neurons (52 pA/pF vs. 37 pA/pF).Conversely, I K current density was smaller in glandular and muscular neurons without ATP and GTP (17 pA/pF and 31 pA/pF, respectively) comparing to cells with ATP and GTP (57 pA/pF and 58 pA/pF, respectively). In glandular (15.5 nA/ms vs. 6.9 nA/ms) and muscular (10.9 nA/ms vs. 7.5 nA/ms) neurons, the I Af activated faster in the absence of ATP and GTP. Half inactivation voltage of I Af in glandular (−110.0 mV vs. −119.7 mV) and muscular (−108.4 vs. −117.3 mV) neurons was shifted towards depolarization in the absence of ATP and GTP. We suggest that the kinetic properties of K+ currents in glandular and muscular sympathetic neurons change markedly in the absence of ATP and GTP in the cytoplasm. Effectiveness of steady-state inactivated currents (I Af and IAS) increased, while effectiveness of steady-state noninactivated currents decreased in the absence of ATP and GTP. The effects were more pronounced in glandular than in muscular neurons. [Copyright &y& Elsevier]

Abstract This paper presents the kinetic and pharmacological properties of voltage-gated K+ currents in anatomically identified glandular postganglionic sympathetic neurons isolated from the superior cervical ganglia in rats. The neurons were labelled by injecting the fluorescent tracer Fast Blue into the submandibular gland. The first group of neurons remained intact, i.e. innervated by the preganglionic axons until the day of current recordings (control neurons). The second group of neurons was denervated by severing the superior cervical trunk 4–6 weeks prior to current recordings (decentralized neurons). In every control and decentralized neuron three categories of voltage-dependent K+ currents were found. (i) The I Af K+ current, steady state, inactivated at hyperpolarized membrane potentials. This current was fast activated and fast time-dependently inactivated, insensitive to TEA and partially depressed by 4-AP. (ii) The I As K+ current, which was steady-state inactivated at less hyperpolarized membrane potentials than I Af . The current activation and time-dependent inactivation kinetics were slower than those of I Af . I As was blocked by TEA and partially inhibited by 4-AP. (iii) The I K K+ current did not undergo steady-state inactivation. In decentralized compared to control neurons the maximum I Af K+ current density (at +50 mV) increased from 116.9 ± 8.2 to 189.0 ± 11.5 pA/pF, the 10–90% current rise time decreased from 2.3 to 0.7 ms and the recovery from inactivation was faster. Similarly, in decentralized compared to control neurons the maximum I As K+ current density (at +50 mV) increased from 49.9 ± 3.5 to 74.3 ± 5.0 pA/pF, the 10–90% current rise time shortened from 29 to 16 ms and the recovery from inactivation of the current was also... [ABSTRACT FROM AUTHOR]

The aim of this perforated-patch study was to test the effect of isoproterenol on the membrane potential in mPFC (medial prefrontal cortex) pyramidal neurons. Isoproterenol depolarized the membrane potential recorded from the soma. This effect was absent in the presence of metoprolol, suggesting the involvement of beta1-adrenergic receptors. The adenylate cyclase activator forskolin also depolarized the membrane potential. Moreover, the effect of isoproterenol was abolished by the adenylate cyclase inhibitor SQ 22536. This suggested that adenylate cyclase was involved in mediating the effect of the beta-adrenergic receptor agonist. The isoproterenol-induced depolarization persisted after inhibition of protein kinase A with H-89. The effect of beta-adrenergic receptor activation on the membrane potential was dependent on Ih channels because it was abolished in the presence of the Ih channel inhibitor ZD 7288. Dendritic recordings were also performed. In the dendritic segments between 100 microm and 150 microm from the soma and between 200 microm and 250 microm from the soma, isoproterenol also depolarized the membrane potential. The magnitude of the beta-adrenergic receptor-stimulated depolarization was the same in the soma and in both dendritic localizations. The depolarization exerted by isoproterenol may influence PFC cognitive functions.

The medial prefrontal cortex (PFC) is involved in cognitive functions, which undergo profound changes during adolescence. This alteration of the PFC function derives from neuron activity, which, in turn, may depend on age-dependent properties and the expression of neuronal ion channels. BK-type channels are involved in controlling both the Ca(+) (+) ion concentration in the cell interior and cell excitability. The purpose of this study was to test the properties of BK currents in the medial PFC pyramidal neurons of young (18- to 22-day-old), adolescent (38- to 42-day-old), and adult (60- to 65-day-old) rats. Whole-cell currents evoked by depolarizing voltage steps were recorded from dispersed medial PFC pyramidal neurons. A selective BK channel blocker - paxilline (10 μM) - irreversibly decreased the non-inactivating K(+) current in neurons that were isolated from the young and adult rats. This current was not significantly affected by paxilline in the neurons obtained from adolescent rats. The properties of single-channel K(+) currents were recorded from the soma of dispersed medial PFC pyramidal neurons in the cell-attached configuration. Of the K(+) channel currents that were recorded, ~90% were BK and leak channel currents. The BK-type channel currents were dependent on the Ca(+) (+) concentration and the voltage and were inhibited by paxilline. The biophysical properties of the BK channel currents did not differ among the pyramidal neurons isolated from young, adolescent, and adult rats. Among all of the recorded K(+) channel currents, 38.9, 12.7, and 21.1% were BK-type channel currents in the neurons isolated from the young, adolescent, and adult rats, respectively. Furthermore, application of paxilline effectively prolonged the half-width of the action potential in pyramidal neurons in slices isolated from young and adult rats but not in neurons isolated from adolescent rats. We conclude that the availability of BK channel currents decreases in medial PFC pyramidal neurons of adolescent rats compared with those in the neurons of young and adult rats while their properties did not change across ages.

This study assesses the effects of ATP and GTP on the kinetic properties of voltage-gated K+ currents in anatomically identified postganglionic sympathetic neurons innervating the submandibular gland and the masseter muscle in rats. Three types of K+ currents were isolated: the I(Af) steady-state inactivating at more hyperpolarized potentials, I(As) steady-state inactivating at less hyperpolarized potentials than I(Af) and the I(K) current independent of membrane potential. The kinetic properties of these currents were tested in neurons with ATP (4 mM) and GTP (0.5 mM) or without ATP and GTP in the intracellular solution. In glandular and muscular neurons in the absence of ATP and GTP in the intracellular solution, the current density of I(Af) was significantly larger (142 pA/pF and 166 pA/pF, respectively) comparing to cells with ATP and GTP (96 pA/pF and 100 pA/pF, respectively). The I(As) was larger only in glandular neurons (52 pA/pF vs. 37 pA/pF).Conversely, I(K) current density was smaller in glandular and muscular neurons without ATP and GTP (17 pA/pF and 31 pA/pF, respectively) comparing to cells with ATP and GTP (57 pA/pF and 58 pA/pF, respectively). In glandular (15.5 nA/ms vs. 6.9 nA/ms) and muscular (10.9 nA/ms vs. 7.5 nA/ms) neurons, the I(Af) activated faster in the absence of ATP and GTP. Half inactivation voltage of I(Af) in glandular (-110.0 mV vs. -119.7 mV) and muscular (-108.4 vs. -117.3 mV) neurons was shifted towards depolarization in the absence of ATP and GTP. We suggest that the kinetic properties of K+ currents in glandular and muscular sympathetic neurons change markedly in the absence of ATP and GTP in the cytoplasm. Effectiveness of steady-state inactivated currents (I(Af) and I(AS)) increased, while effectiveness of steady-state noninactivated currents decreased in the absence of ATP and GTP. The effects were more pronounced in glandular than in muscular neurons.

Pain is generated by activation of specific dorsal root ganglion (DRG) neurons termed the nociceptive neurons. The nociceptive DRG neurons express 3 categories of ionic channels a. channels gated by pain stimuli, b. channels responsible for the transmission of information from sensory receptors to the spinal cord, c. channels responsible for the release of neurotransmitters in the spinal cord. There is evidence that kinetic properties, molecular structure and functional significance of the ionic channels expressed in nociceptive DRG neurons are different compared to the other types of DRG neurons. The ionic channels are strictly controlled by receptors for neurotransmitters expressed in the plasma membrane of nociceptive DRG neurons.