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V I Pidoplichko

Publications and source records attributed to V I Pidoplichko.

At least 19 recordsLinked to original sources
PubMed2000

Variations in desensitization of nicotinic acetylcholine receptors from hippocampus and midbrain dopamine areas.

This study addresses two issues arising from the desensitization of nicotinic acetylcholine receptors from the hippocampus, ventral tegmental area, and substantia nigra. First, biophysical studies can find potent and complete desensitization of nicotinic receptors; but in vivo studies often find that desensitization affecting a behavior is less than complete, or that desensitization is important over a different nicotine concentration range. Our results show that there can be significant differences in desensitization when comparing nearby neurons from the same area of the brain. Thus, nicotinic receptors on a minority of neurons may remain active and maintain a behavior under conditions that can produce significant desensitization. Second, agonist applications that are intended to active nicotinic receptors also cause desensitization. The prevailing conditions and the rate of agonist application and removal will control the degree of activation vs. desensitization. These and other factors regulate the efficacy of nicotinic agonists experimentally and physiologically.

Animals↗
PubMed1997

Nicotine activates and desensitizes midbrain dopamine neurons.

Tobacco use in developed countries is estimated to be the single largest cause of premature death. Nicotine is the primary component of tobacco that drives use, and like other addictive drugs, nicotine reinforces self-administration and place preference in animal studies. Midbrain dopamine neurons normally help to shape behaviour by reinforcing biologically rewarding events, but addictive drugs such as cocaine can inappropriately exert a reinforcing influence by acting upon the mesolimbic dopamine system. Here we show that the same concentration of nicotine achieved by smokers activates and desensitizes multiple nicotinic receptors thereby regulating the activity of mesolimbic dopamine neurons. Initial application of nicotine can increase the activity of the dopamine neurons, which could mediate the rewarding aspects of tobacco use. Prolonged exposure to even these low concentrations of nicotine, however, can cause desensitization of the nicotinic receptors, which helps to explain acute tolerance to nicotine's effects. The effects suggest a cellular basis for reports that the first cigarette of the day is the most pleasurable, whereas the effect of subsequent cigarettes may depend on the interplay between activation and desensitization of multiple nicotinic receptors.

Acetylcholine↗
PubMed1996

Fast desensitizing kainate-gated current resolved in whole-cell experiments on isolated rat hippocampal neurons.

In whole-cell concentration-jump experiments on dissociated rat hippocampal neurons the existence of a fast desensitizing component of a kainate-gated current was demonstrated. More than 90% of all neurons tested possessed such a receptor. Electrophysiological and pharmacological data suggest an association of this fast kainate-gated current with that mediated through a combination of subunits forming a low-affinity "(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)-preferring' receptor. Kinetic data suggest the existence of a compact spatial location of fast desensitizing "AMPA-preferring' receptors which are naturally expressed on the surface of the neurons. An AMPA-insensitive current component mediated through fast desensitizing high-affinity kainate receptors was not observed.

Animals↗
PubMed1996

Dependence of solution exchange time on cell or patch linear dimensions in concentration jump experiments using patch-clamped sensory neurones.

A critical evaluation of "concentration jump" techniques employing hydrodynamic solution exchange has been undertaken. Data obtained from experiments using acutely isolated sensory neurones demonstrated a dependence of the total solution exchange time on the linear dimensions of the preparation. The exchange time around a circular surface is proportional to the radius of this surface. A quantitative approximation can be formulated as follows: if the membrane area of the object under investigation is increased n times, the duration of the full solution exchange is increased by radical n times. A nonlinear dependence of exchange time on vacuum pressure was confirmed in a separate set of experiments.

Animals↗
PubMed1995

Preferential block of desensitizing AMPA receptor in hippocampal neurons by gamma-D-glutamylaminomethylsulfonic acid.

The (RS)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolopropionic acid (AMPA)/kainate receptor-channel complex mediates fast components of excitatory synaptic currents in the central nervous system. Distinguishing between these components is a difficult pharmacological task. As was recently reported, gamma-D-glutamylaminomethylsulfonic acid (GAMS) may be a selective kainate receptor antagonist. We have tested this possibility in experiments which were carried out on acutely isolated rat hippocampal neurons. It appeared that 1 mM GAMS first blocked 83 +/- 1% of the fast desensitizing 128 microM AMPA-gated current, but only 38 +/- 6% of the non-desensitizing current component and reached, at higher GAMS concentrations, a plateau at about 50% of the control steady state current level. In contrast to the blocking action of GAMS on AMPA-gated currents, 4-fold higher concentrations of GAMS were needed to block currents elicited by 256 microM kainate application. It is suggested that several subunit compositions of the AMPA-gated receptor could coexist on a single hippocampal cell. Furthermore, GAMS has a certain preference for subunit assemblies which could mediate fast desensitizing and, a portion of, the non-desensitizing current component.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Abscisic acid potentiates NMDA-gated currents in hippocampal neurones.

NMDA receptor functioning underlies the basic mechanism of synaptic plasticity of the central nervous system. The NMDA receptor is a subject for modulation by certain substances: facilitation of this receptor is thought to be crucial for the induction of plasticity phenomena. In the present investigation evidence for a potentiation of the NMDA-receptor by trans,trans-abscisic acid (postulated endogenous substance) is provided. Pre-exposure to trans,trans-abscisic acid induced a marked increase mainly of the fast component of NMDA-gated currents in isolated rat hippocampal neurones. The potentiating effect depended on an extracellular trans,trans-abscisic acid concentration with an EC50 value about 440 microM, Hill coefficient 2. Such a facilitatory effect developed rather slowly with a time constant of about 3 s. The results obtained imply the existence of a novel mechanism of NMDA receptor potentiation. The data presented indicate a possible neurophysiological significance of abscisin.

Abscisic Acid↗
PubMed1994

Metabotropic glutamate receptor agonist DCG-IV as NMDA receptor agonist in immature rat hippocampal neurons.

The electrophysiological action of (2S,1'R;2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV) on the NMDA receptor was investigated with the help of concentration-jump experiments on freshly dissociated hippocampal CA1 and CA3 neurons of rats. Inward currents elicited by a pulse of DCG-IV were insensitive to 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and could be blocked by D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5) and magnesium and enhanced by glycine. The substance displayed cross-desensitization with NMDA but not with kainate or (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). Dose-response curves showed that DCG-IV was weaker than NMDA but more potent than glutamate in eliciting agonist-gated currents. From these data we conclude that DCG-IV has to be used with caution as a tool for the investigation of metabotropic glutamate receptors.

2-Amino-5-phosphonovalerate↗
PubMed1992

Ammonia and proton gated channel populations in trigeminal ganglion neurons.

The existence of three distinct types of proton-gated sodium currents classified in accordance with their kinetics of desensitization as fast, medium and slow, has been confirmed in the present study on isolated rat trigeminal ganglion neurons. The emphasis was put on the investigation of a peculiar medium type of a chemically gated channel population, using the concentration jump method. The features of the medium-type mechanism allow to distinguish it from the other already known types: it was insensitive to the Ca antagonist verapamil (in contrast to proton-gated sodium current found in dorsal root ganglion neurons), displayed a strong dependence of the kinetics of desensitization on the membrane potential, and (besides the apparent proton-gating) was activated and desensitized by the application of ammonia containing solution at normal pH values. The effect of ammonia itself appeared to be a good tool for the separation of fast and slow proton-gated responses. The results obtained allow to postulate a nonspecific proton-activation of medium-type receptor-channel complexes and their specificity to ammonia (Kd = 10(-4) mol/l) as an agonist.

Ammonia↗
PubMed1990

[The effect of the acidification of the extracellular medium on the membrane sodium currents of single heart cells].

The effect of a drop of extracellular pH on the fast and slow sodium currents (INaf and INas) was studied in the rat isolated perfused ventricular myocytes. The shift of the extracellular pH value from 7.4 to 5.0 caused a disappearance of INaf. If the fast sodium current was blocked by external tetrodotoxin (10(-6) mol/l) or inactivated by the shift of the maintaining potential from -120 to -70 mV. the external pH drop from 7.4 to 5.0 only caused a slight diminishing of the slow sodium current amplitude. INas kinetics and potential-dependent properties were unaffected. INas was blocked at the external pH values lower than 4.0. The data obtained suggests that INaf and INas of isolated single cardiomyocytes have a different sensitivity to external pH: INaf is more sensitive to the acidification of the external medium than INas.

Animals↗
PubMed1987

Possible existence of transient TTX-sensitive chloride current in the membrane of isolated cardiomyocytes.

Cardiomyocytes enzymatically isolated from rat and guinea pig ventricular tissue were investigated under conditions of intracellular perfusion and voltage clamp at 18-20 degrees C. Perfusion with 135 mmol/l Tris(HF), pH 7.2 was used to eliminate outward potassium currents. The dependence of inward current (elicited by depolarizing pulses from a holding potential level of--120 mV) on low external TTX concentrations (from 10(-13) to 10(-10) mol/l) was studied. Similar TTX concentrations increased the amplitude of the inward current and changed its kinetics in a large number of cells tested. The effect was fully reversible. The effect could be evaluated in a net form by digital subtraction of the current obtained after the application of a low external TTX concentration from the initial current in a TTX-free solution. The TTX concentration dependence of the difference current could be fitted by one-to-one binding curve with Kd = (1.0 +/= 0.4) x 10(-12) mol/l. TTX-induced current changes were absent in low sodium or chloride-free external solutions. The outward current (a block of which by TTX produced the inward current changes observed) showed a reversal potential consistent with the chloride nature of such a current. The existence of a transient TTX-sensitive Na-dependent potential gated chloride current in the membrane of isolated cardiomyocytes is postulated.

Animals↗
PubMed1987

Sodium currents in the membrane of isolated cardiomyocytes.

In the experiments on ventricular myocytes which were enzymatically isolated from hearts of 4 weeks old rats and were internally perfused in voltage clamp conditions the existence of two sodium currents was demonstrated. The data obtained suggest that the so called fast sodium current in the membrane of ventricular myocytes is in fact a sum of two currents with different kinetics and potential dependent properties, sensitivity to tetrodotoxin and external pH which are supposed to be passed through separate membrane channel populations. Due to about four fold difference in their time courses of inactivation the currents were called fast sodium current (IfNa) and slow sodium current (IsNa).

Animals↗
PubMed1986

[Effect of tetrodotoxin in low concentrations on the ion currents of trigeminal ganglion neurons in the rat].

Isolated neurons from trigeminal ganglia of one-month-old rats were studied under conditions of intracellular perfusion and voltage clamp. Increase of the inward current amplitude and deceleration of current decay due to the action of low external concentrations of tetrodotoxin (10(-12)-10(-10) M) were observed in a number of the cells tested. Such changes were absent in chloride-free extracellular solution. The existence of a transient potential-dependent current carried by chloride anions through tetrodotoxin-sensitive chloride channels in the membrane of trigeminal ganglion neurons is postulated.

Animals↗
PubMed1986

Two different tetrodotoxin-separable inward sodium currents in the membrane of isolated cardiomyocytes.

Isolated ventricular myocytes of 3 to 5 weeks old rats were studied under conditions of intracellular perfusion and voltage clamp. The existence of two inward sodium currents with different TTX-sensitivities and different properties was shown. The fast sodium current was more sensitive to TTX (Kd about 8 X 10(-8) mol/l). The block of the slow sodium current by TTX was less specific (Kd about 7 X 10(-6) mol/l). There was an about four fold difference in the inactivation time constants between these currents. The maximum on the I-V curve of the slow sodium current was shifted along the voltage axis by about 15 mV in the positive direction as compared with that of the fast sodium current. A slow current carried by calcium ions was observed in sodium-free solution. The kinetics and TTX-sensitivity of this current were similar to those of the slow sodium current. The amplitude of this current was 15 to 20 times lower as compared with the slow sodium current observed in Na-containing solution with 10(-6) mol/l TTX (a concentration which completely blocked the fast sodium current). It is suggested that the slow voltage-gated TTX-sensitive channels described are not highly selective and pass both sodium and calcium ions.

Animals↗
PubMed1983

Receptor for ATP in the membrane of mammalian sensory neurones.

ATP-activated conductance has been found in a large number of neurones isolated from various sensory ganglia of the rat and cat. The inward current produced by ATP (Kd = 5 x 10(-6) M) is carried by cations and demonstrates rapid activation and slow desensitization. The sequence of agonists (ATP greater than ADP with AMP and adenosine ineffective) is different from those previously described for purinergic receptors P1 and P2.

Adenosine Triphosphate↗
PubMed1981

A "receptor" for protons in small neurons of trigeminal ganglia: possible role in nociception.

Neurons of the rat's trigeminal ganglion were enzymatically isolated and investigated under the conditions of intracellular perfusion and voltage clamp. Recently discovered proton-activated sodium conductance was found in about half of the neurons. The majority of these proton-sensitive neurons (74%) were less than 26 micrometer in diameter, whereas most of the proton-insensitive cells (75%) were larger than 26 micrometer in diameter. The possibility is discussed that the small proton-sensitive neurons may participate in nociception.

Animals↗