Biomedical subjects

M Pessia

Publications and source records attributed to M Pessia.

5 recordsLinked to original sources

PubMed1995

Contributions of the C-terminal domain to gating properties of inward rectifier potassium channels.

Two inward rectifier potassium channels, the G protein-dependent GIRK1 and the G protein-independent BIR10, display large differences in rectification and macroscopic kinetics. A chimeric channel was constructed in which the putative intracellular carboxy-terminal domain of the G protein-dependent channel replaced the corresponding domain of the G protein-independent channel. The chimeric channel conducted potassium ions without the requirement of activated G proteins, yet displayed activation and deactivation kinetics and rectification properties similar to those of the G protein-dependent channel. The results demonstrate that structural elements in the C-terminus can independently control gating but not G protein signal transduction. The voltage dependence, time course, and kinetics of gating suggest a mechanism in which the pore may be occluded by reversible interactions with charged residues in the C-terminus.

Amino Acid Sequence↗

PubMed1994

Actions of 5-hydroxytryptamine on ventral tegmental area neurons of the rat in vitro.

Intracellular recordings were made with conventional microelectrodes and with whole-cell patch-clamp electrodes from neurons of the rat ventral tegmental area and substantia nigra zona compacta in vitro. Neurons were distinguished as principal cells and secondary cells; it is known from previous work that most principal cells contain dopamine whereas secondary cells do not. 5-Hydroxytryptamine (5-HT; 3-100 microM) depolarized (or evoked an inward current at -60 mV) 46% of 153 principal cells; a small proportion (11%) of cells were hyperpolarized (or showed outward current at -60 mV). Secondary cells were equally likely to be depolarized (or inward current at -60 mV, 30% of 80 cells) or hyperpolarized (or outward current at -60 mV, 28%). approximately 40% of each type of cell were unaffected by 5-HT. Depolarizing responses of 5-HT were mimicked by (+/-)-1-(2,5-dimethoxy-4-iodophenyl)- 2-aminopropane (DOI) and blocked by ketanserin. Hyperpolarizing responses were mimicked by dipropyl-5-carboxamidotryptamine and reversed polarity at the K+ equilibrium potential. Inhibitory postsynaptic potentials (or currents) mediated at GABAA receptors occurred spontaneously in some principal cells; they were reversibly blocked by tetrodotoxin and bicuculline. 5-HT either increased or decreased the frequency of these synaptic potentials but did not change their mean amplitude or decay time.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamines↗

PubMed1994

Neurotensin excitation of rat ventral tegmental neurones.

1. Whole-cell patch-clamp recordings were made from ventral tegmental area neurones in rat midbrain slices in vitro. In principal cells, which are presumed to contain dopamine, neurotensin (< or = 1 microM) caused an inward current at -60 mV in thirty of forty-seven neurones and had no effect on the remainder. In secondary neurones, neurotensin caused an inward current in twelve of thirty-three cells. 2. The inward current evoked by neurotensin reached a maximum amplitude of about 80 pA, and declined over several minutes when the application was discontinued. The current was most commonly accompanied by a decrease in membrane conductance and reversed polarity at a strongly hyperpolarized potential; this reversal potential was less negative in a higher extracellular potassium concentration. Neurotensin also caused an inward current even in potassium-free internal and external solutions; this current was accompanied by a conductance increase, reversed close to 0 mV and was inhibited by reduction of the extracellular sodium concentration (from 150 to 20 mM). 3. The inward current was associated with a large increase in noise; this persisted in calcium-free solutions but was inhibited by low sodium concentration. The increase in noise was more prominent at hyperpolarized potentials. The amplitude of the unitary current underlying the increase in noise was estimated from the ratio of the variance to the mean as about 1.5 pA at -100 mV. 4. When the recording was made with an electrode containing guanosine 5'-thio-triphosphate, the steady inward current evoked by neurotensin did not reverse when the application was discontinued. When the recording electrode contained pertussis toxin, the action of neurotensin was not different although outward currents evoked by dopamine and baclofen declined with time. 5. It is concluded that neurotensin excites ventral tegmental area neurones by activating a pertussis toxin-insensitive guanosine nucleotide-binding protein. This leads to a reduction in membrane potassium conductance and an increase in membrane sodium conductance, the relative contribution of which varies from cell to cell.

Amino Acid Sequence↗

PubMed1994

Cloning and expression of a family of inward rectifier potassium channels.

Five new members of the two-transmembrane domain potassium channel family have been identified from rat brain, heart and skeletal muscle. The channel mRNAs are differentially expressed and found in both the central nervous system and periphery. Expression of two of these channels in Xenopus oocytes gave rise to inwardly rectifying potassium currents which were voltage-dependently blocked by barium and cesium. Voltage command pulses negative to Ek evoked inward currents which rapidly reached a peak amplitude and relaxed to a steady-state level. The quantity of current relaxation differed in the two channels and was increased at more negative potentials. The degree of current rectification was also different for the two channels. The results demonstrate the existence of a large and widely expressed family of inward rectifier potassium channel subunits with distinct tissue distributions and functional properties.

Amino Acid Sequence↗

PubMed1992

Chronic treatment with DAU 6215, a new 5-HT3 receptor antagonist, causes a selective decrease in the number of spontaneously active dopaminergic neurons in the rat ventral tegmental area.

Electrophysiological techniques were used to study the effects of the new compound, DAU 6215 ((3-alpha-tropanyl) 1H-benzimidazolone-3-carboxamide chloride), a selective 5-HT3 receptor antagonist, on the activity of dopamine (DA)-containing neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA). Acute i.v. injections of DAU 6215 did not cause any change in the basal firing rate of DA neurons in the SNc or in the VTA. Pretreatment with DAU 6215 did not modify the inhibitory effect of apomorphine on the firing rate of midbrain DA neurons. Acute s.c. administration of DAU 6215 caused a significant increase in the number of spontaneously active DA neurons in the VTA but not in the SNc. This effect was similar to that of acute clozapine, whereas acute haloperidol caused a significant increase of spontaneously active DA neurons in both the SNc and the VTA. Repeated consecutive s.c. administration of DAU 6215 and clozapine for 21 days produced a significant decrease in the number of spontaneously active DA neurons in the VTA but not in the SNc. Chronic haloperidol (21 days) decreased the number of DA cells both in the SNc and VTA. The effect of chronic DAU 6215 on the activity of VTA DA neurons was reversed by apomorphine, suggesting that these neurons were probably under a state of depolarization block. These findings indicate that DAU 6215 may have potential antipsychotic activity, probably associated with a low incidence of extrapyramidal side-effects.

Animals↗