Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Dissociated neurones from embryonic rat hypothalamus were grown for several weeks in culture where they formed complex networks. These synaptically coupled networks were capable of generating synchronized bursting activity. Voltage-activated membrane currents were studied in these neurones using a patch clamp in the whole-cell configuration. 2. Outward currents were carried by K+ ions and consisted of an inactivating and a non-inactivating component. These components were similar to the transient K+ current (IA) and the delayed rectifier current (IK) reported in neurones from the postnatal rat hypothalamus. Application of Zn2+ (1 mM) blocked the transient component completely while reducing the non-inactivating component by only approximately 20%. 3. Inward currents were carried by Na+ and Ca2+ ions. Rapidly activating transient Na+ currents were activated at approximately -25 mV. TTX entirely blocked these currents at low concentration (300 nM). Voltage sensitivity of the Na+ conductance was 5.8 mV per e-fold change with half-maximal activation occurring at -8 mV. Na+ current kinetics could be well described by the Hodgkin-Huxley model (m3h). 4. With depolarizing pulses from a holding potential of -80 mV two Ca2+ current components with different ranges of activation were identified. Low voltage-activated (LVA, T-type) Ca2+ currents were activated at approximately -50 mV. High voltage-activated (HVA; also called L- or N-type) Ca2+ currents were observed at membrane potentials more positive to approximately -30 mV. LVA Ca2+ currents were observed in hypothalamic neurones that had developed a network of dendritic processes in the course of several weeks in culture. Activation and inactivation time constants of LVA Ca2+ currents were 15-25 ms and 30-100 ms (-30 to -45 mV). In contrast to HVA Ca2+ currents, no LVA Ca2+ currents were seen in neuronal somata obtained from the network cultures by mechanical dissociation. This suggests that most of the LVA Ca2+ channels are located on the dendritic tree rather than on the soma membrane. 5. HVA Ca2+ currents were maximal between 0 and +10 mV (external [Ca2+] = 5 mM). The time-to-peak was in the range of 1.7-5.4 ms (+30 to -10 mV). Tail currents following repolarization decayed monoexponentially with a time constant of approximately 210 microseconds. During 500 ms depolarizations, 90% of the current inactivated. The time course of inactivation showed two time constants of approximately 40 and approximately 700 ms.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ionic currents in cultured rat hypothalamic neurones. 133 25

Action potentials generated by voltage-dependent Ca2+ conductances were studied at 25 degrees C with the perforated-patch technique, in freshly dispersed adult rat sensory neurons perfused with Na-free solutions containing tetraethylammonium. Brief depolarizing currents from membrane potentials negative to - 75 mV always elicited long (> 100 ms) plateau spikes which had different thresholds in different neurons: a low threshold around - 60/- 50 mV and a high-threshold at - 30/- 20 mV. Stimulations from potentials positive to - 55 mV, on the contrary, elicited spikes originating only in the high threshold region and sensitive to 25 microM Cd2+, designated high-threshold spikes. In neurons which showed spikes with low threshold, addition of 25 microM Cd2+ disclosed a smaller and shorter regenerative response, the low-threshold spike. Moreover, the classical 'anode-break' stimulation from - 50/- 60 mV uncovered isolated low-threshold spikes, indicating a time- and voltage-dependent de-inactivating process. From the properties of the low (LVA) and high (HVA) voltage-activated Ca2+ currents, recorded under the same extracellular conditions, a Hodgkin - Huxley model was derived and used to reconstruct all the features of the recorded spikes. The model was also able to simulate experimental blocking of LVA channels by amiloride, modulation of HVA channels by baclofen and induced oscillatory firing. This agreement between the behaviour of recorded spikes and their mathematical description led us to conclude that the LVA and HVA Ca2+ currents underlie the low- and high-threshold Ca2+ spikes, respectively. Furthermore, our data suggest that complex behaviour known to be typical of central nervous system neurons is also present in sensory peripheral neurons.
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PMID:A Quantitative Description of Low- and High-threshold Ca2+ Spikes in Rat Sensory Neurons: A Perforated-patch Study. 1210 16

The olfactory bulb of mammals contains a large population of dopaminergic interneurones within the glomerular layer. Dopamine has been shown both in vivo and in vitro to modulate several aspects of olfactory information processing, but the functional properties of dopaminergic neurones have never been described due to the inability to recognize these cells in living preparations. To overcome this difficulty, we used a transgenic mouse strain harbouring an eGFP (enhanced green fluorescent protein) reporter construct under the promoter of tyrosine hydroxylase, the rate-limiting enzyme for cathecolamine synthesis. As a result, we were able to identify dopaminergic neurones (TH-GFP cells) in living preparations and, for the first time, we could study the functional properties of such neurones in the olfactory bulb, in both slices and dissociated cells. The most prominent feature of these cells was the autorhythmicity. In these cells we identified five main voltage-dependent conductances: the two having largest amplitude were a fast transient Na(+) current and a delayed rectifier K(+) current. In addition, we observed three smaller inward currents, sustained by Na(+) ions (persistent type) and by Ca(2)(+) ions (LVA and HVA). Using pharmacological tools and ion substitution methods we showed that the pacemaking process is supported by the interplay of the persistent Na(+) current and of a T-type Ca(2)(+) current. We carried out a complete kinetical analysis of the five conductances present in these cells, and developed a Hodgkin-Huxley model of TH-GFP cells, capable of reproducing accurately the properties of living cells, including autorhytmicity, and allowing a precise understanding of the process.
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PMID:Functional properties of dopaminergic neurones in the mouse olfactory bulb. 1573 Nov 85