Biomedical subjects

Paweł Szulczyk

Publications and source records attributed to Paweł Szulczyk.

7 recordsLinked to original sources

PubMed2006

Opioid mu receptor activation inhibits sodium currents in prefrontal cortical neurons via a protein kinase A- and C-dependent mechanism.

Opioid transmission in the medial prefrontal cortex is involved in mood regulation and is altered by drug dependency. However, the mechanism by which ionic channels in cortical neurons are controlled by mu opioid receptors has not been elucidated. In this study, the effect of mu opioid receptor activation on voltage-dependent Na(+) currents was assessed in medial prefrontal cortical neurons. In 66 out of 98 nonpyramidal neurons, the application of 1 microM of DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-OL]-enkephalin), a specific mu receptor agonist, caused a decrease in the Na(+) current amplitude to approximately 79% of that observed in controls (half blocking concentration = 0.094 microM). Moreover, DAMGO decreased the maximum current activation rate, prolonged its time-dependent inactivation, and shifted the half inactivation voltage from -63.4 mV to -71.5 mV. DAMGO prolonged the time constant of recovery from inactivation from 5.4 ms to 7.4 ms. The DAMGO-evoked inhibition of Na(+) current was attenuated when GDP-beta-S (0.4 mM, Guanosine 5-[beta-thio]diphosphate trilithium salt) was included in the intracellular solution. Inhibitors of kinase A and C greatly attenuated the DAMGO-induced inhibition, while adenylyl cyclase and kinase C activators mirrored the DAMGO inhibitory effect. Na(+) currents in pyramidal neurons were insensitive to DAMGO. We conclude that the activation of mu opioid receptors inhibits the voltage-dependent Na(+) currents expressed in nonpyramidal neurons of the medial prefrontal cortex, and that kinases A and C are involved in this inhibitory pathway.

Adenylyl Cyclases↗

PubMed2005

Effects of ATP and GTP on voltage-gated K+ currents in glandular and muscular sympathetic neurons.

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.

Adenosine Triphosphate↗

PubMed2003

Postdecentralization plasticity of voltage-gated Na+ currents in rat glandular sympathetic neurons.

The kinetic properties of voltage-gated Na(+) currents in two groups of glandular postganglionic sympathetic neurons were assessed. The first group of neurons remained innervated by preganglionic axons until the day of current recordings, while the second--decentralized 4 weeks prior to recordings. An increase of maximum current amplitude and density was noted in decentralized neurons. Na(+) currents activated and time-dependently inactivated more slowly in decentralized than in control neurons. Furthermore, after decentralization the currents steady-state inactivated at less hyperpolarized potentials as well as reactivated faster from inactivation. We conclude that the Na(+) currents in decentralized postganglionic glandular sympathetic neurons undergo up-regulation.

Amidines↗

PubMed2003

Postdecentralization plasticity of voltage-gated K+ currents in glandular sympathetic neurons in rats.

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 IK 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 faster. The maximum density (at +50 mV) of I(K) in decentralized compared to control neurons decreased from 76.6 +/- 3.9 to 60.7 +/- 6.3 pA/pF. We suggest that the upregulation of voltage-gated time-dependently-inactivated K(+) currents and their faster recovery from inactivation serve to restrain the activity of glandular sympathetic neurons after decentralization.

4-Aminopyridine↗

PubMed2002

Expression and kinetic properties of Na(+) currents in rat cardiac dorsal root ganglion neurons.

The expression and properties of voltage-gated Na(+) currents in cardiac dorsal root ganglion (DRG) neurons were assessed in this study. Cardiac DRG neurons were labelled by injecting the Fast Blue fluorescent tracer into the pericardium. Recordings were performed from 138 cells. Voltage-dependent Na(+) currents were found in 115 neurons. There were 109 neurons in which both tetrodotoxin-sensitive (TTX-S, blocked by 1 microM of TTX) and tetrodotoxin-resistant (TTX-R, insensitive to 1 microM of TTX) Na(+) currents were present. Five cells expressed TTX-R current only and one cell only the TTX-S current. The kinetic properties of Na(+) currents and action potential waveform parameters were measured in neurons with cell membrane capacitance ranging from 15 to 75 pF. The densities of TTX-R (110.0 pA/pF) and TTX-S (126.1 pA/pF) currents were not significantly different. Current threshold was significantly higher for TTX-R (-34 mV) than for TTX-S (-40.4 mV) currents. V(1/2) of activation for TTX-S current (-19.6 mV) was significantly more negative than for TTX-R current (-9.2 mV), but k factors did not differ significantly. V(1/2) and the k constant for inactivation for TTX-S currents were -35.6 and -5.7 mV, respectively. These values were significantly lower than those recorded for TTX-R current for which V(1/2) and k were -62.3 and -7.7 mV, respectively. The action potential threshold was lower, the 10-90% rise time and potential width were shorter before than after the application of TTX. Based on this we drew the conclusion that action potential recorded before adding tetrodotoxin was mainly TTX-S current dependent, while the action potential recorded after the application of toxin was TTX-R current dependent. We also found 23 cells with mean membrane capacitance ranging from 12 to 35 pF (the smallest labelled DRG cells found in this study) that did not express the Na(+) current. The function of these cells is unclear. We conclude that the overwhelming majority of cardiac dorsal root ganglion neurons in which voltage-dependent Na(+) currents were present, exhibited both TTX-S and TTX-R Na(+) currents with remarkably similar expression and kinetic properties.

Action Potentials↗

PubMed2002

[Nociceptive 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.

Animals↗

PubMed1994

Influence of morphine on the activity of low-threshold visceral mechanoreceptors in cats with acute pericarditis.

The purpose of this investigation was to test whether morphine (morphinum hydrochloricum) applied to the receptive field of the thoracic visceral afferent fibres modifies their activity. Experiments were performed on chloralose-anaesthetised cats, paralysed and artificially ventilated, in a state of pericarditis that was induced by intrapericardial injection of lambda-carrageenan and kaolin. Resulting acute inflammation was proven histopathologically and documented electrocardiographically. Single afferent fibres with receptive fields in thoracic viscera were dissected from thoracic sympathetic chain (19 fibres), as well as the vagus nerve (9 fibres). All tested fibres transmitted sensory information from the low-threshold mechanoreceptors. As a final result, it was found that morphine (0.001-1.0 mg/ml) when applied locally activates, depending on the dose, afferent fibres as follows: 12 sympathetic afferents (out of 12 tested), and 7 vagal afferents (out of 9 tested). In examining the specificity of morphine action, the preliminary local application of naloxone (1.0 mg/ml) just before morphine, blocked all excitatory responses. The excitatory response was present whether the receptive field was located in the inflammatory area, or outside it, in group III or IV fibres.

Acute Disease↗