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Potassium currents in the mammalian sympathetic neurones under voltage-clamp conditions
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A fast transient outward current in the rat sympathetic neurone studied under voltage-clamp conditions.
No full textPost‐ganglionic neurones of the isolated rat superior cervical ganglion were voltage clamped at 37 degrees C using separate intracellular voltage and current micro‐electrodes. Control experiments in current clamp suggested that the neurone is electrotonically compact, the soma and the proximal dendritic membranes being under good spatial voltage uniformity. Depolarizing voltage steps from membrane potentials near ‐50 mV evoked: (i) a voltage‐dependent inward Na+ current, (ii) an inward Ca2+ current, (iii) a voltage‐dependent outward K+ current, (iv) a Ca2+‐activated K+ outward current. Depolarizations from holding potentials more negative than ‐60 mV elicited, besides the currents mentioned above, a fast transient outward current IA which peaked in 1‐2.5 ms and then decayed to zero following an exponential time course. The IA current was shown to be primarily, if not exclusively, carried by K+. It was unaffected by removal of external Ca2+ or addition of Cd2+ and was weakly blocked by tetraethylammonium ions and partially by 4‐aminopyridine. The IA current showed a linear instantaneous current‐voltage relationship. Its activation ranged from ‐60 to 0 mV with a mid‐point at ‐30 mV. The A conductance could be described in terms of a simple Boltzmann distribution for a single gating particle with a valency of +3. Both the development and removal of inactivation followed a single exponential time course with a voltage‐dependent time constant which was large near the resting potential (42 ms at ‐70 mV) and small (11 ms) near ‐100 and ‐40 mV. Steady‐state inactivation h infinity ranged from ‐100 to ‐50 mV, with a mid‐point at ‐78 mV, suggesting that approximately 50% of the IA channels are available at the physiological resting potential. Action potentials elicited from various holding potentials showed maximal repolarization rates dependent on the holding potential itself. This voltage dependence was found to be in reasonably good agreement with that of h infinity curve. These data are consistent with the view that in the rat sympathetic neurone, under physiological conditions, it is the IA current rather than the delayed outward current that is responsible for the fast action potential repolarization. © 1985 The Physiological Societ
Identification of delayed potassium and calcium currents in the rat sympathetic neurone under voltage clamp
No full textPost-ganglionic neurones of the isolated rat superior cervical ganglion were studied at 37 degrees C under two-electrode voltage-clamp conditions. Membrane depolarization beyond -40 mV from holding levels between -50 and -100 mV produced a delayed outward current which exhibited no inactivation within this voltage range. The current is carried primarily by K+ ions and its instantaneous I-V relation is linear. The total outward current could be separated into two distinct components on the basis of ion-substitution experiments. A voltage-dependent component of the delayed current, termed IK(V), is activated by membrane depolarization beyond -40 mV when Ca2+ fluxes are selectively blocked by Cd2+ or in Ca2+-free solution. IK(V) develops following first-order kinetics and rises to a peak with a voltage-dependent delay (239 ms at -30 mV and 23 ms at +10 mV). GK(V) attains a saturating value of the order of 17 mS/cm2 at about +20 mV and can be described in terms of a simple Boltzmann distribution for a single gating particle with a valency equal to +2.5. A second component of the delayed outward current, termed IK(Ca), depends on Ca2+ entry for its activation and was isolated as difference current before and after block of Ca2+ movements across the membrane. IK(Ca) is larger and faster than IK(V): it is strictly related to Ca2+ influx and also depends on membrane potential depolarization. A distinct Ca2+ current, ICa, was recorded from the neurone exposed to Na+-free or tetrodotoxin solution. ICa was activated by membrane depolarization beyond -30 mV and reached a maximum value near 0 mV. Its activation agrees with fourth-order kinetics and becomes faster with increasing depolarization. The Ca2+ current developed with a voltage-dependent time to peak of 2.9-1.8 ms and thereafter completely inactivated. The relationship between ICa and IK(Ca) is discussed. The Ca2+-k+ repolarizing system is expected to be mainly associated with action potentials arising from a depolarized neurone, whereas the IA current (Belluzzi, Sacchi & Wanke, 1985) dominates the repolarization mechanism at the normal membrane potential. The effect of muscarine was examined. Muscarine (10-50 microM) produced a fall in conductance with a voltage dependence similar to that exhibited by GK(Ca) and was ineffective when removing extracellular Ca2+ or adding Cd2+. A partial suppression of ICa by muscarine is demonstrated. It is suggested that the decrease of the outward current magnitude in the presence of muscarine may be accounted for qualitatively by the reduction in ICa
The biophysical properties of beta2-V287L mutant neuronal nicotinic receptors linked to ADNFLE
No full textThe biophysical properties of beta2-V287L mutant neuronal nicotinic receptors linked to ADNFL
A TTX-sensitive conductance underlying burst firing in isolated pyramidal neurons from rat neocortex
No full textPyramidal neurons were acutely isolated from neocortex slices of 14- to 20-day-old rats and patch-clamped under physiological conditions. Current-clamp recordings revealed firing patterns corresponding to those previously reported in slices as regular spiking (RS) and intrinsically bursting (IB), i.e., single action potentials (AP), trains of regular spikes and bursts with depolarizing after-potentials (DAP). In IB neurons, intracellular perfusion with KF blocked the high-voltage-activated Ca2+ and the Ca(2+)-dependent K+ currents, revealing APs with a 10-30 ms shoulder at -35 mV (shoulder AP), which was the supporting plateau of the intraburst spikes. The use of the A channel blocker, 4-aminopyridine, caused a three-fold reduction in the AP repolarizing rate. A study of the de- and repolarizing rates modulating the spike shape (shoulder AP, burst or single APs) suggested that the percentage of available A channels could play a crucial role in burst formation. Blockade of the residual T-type Ca2+ current by Ni2+ did not inhibit the AP shoulder, whereas it was completely and reversibly inhibited by 30 nM TTX, which did not affect AP amplitude. The AP rising rate was only halved by 100 nM TTX. The data concerning the A channel-mediated burst formation and the role of the TTX-sensitive conductance have been successfully simulated in a model cell. We suggest that bursting is an intrinsic property of the membrane of neocortex neurons, and is sustained by TTX-sensitive slowly inactivating and/or persistent Na+ conductances
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Nicotinic acetylcholine receptors and nocturnal frontal lobe epilepsy
No full textSleep has traditionally been recognized as a precipitating factor for some forms of epilepsy, although differential diagnosis between some seizure types and parasomnias may be difficult. Autosomal dominant frontal lobe epilepsy is characterized by nocturnal seizures with hyperkinetic automatisms and poorly organized stereotyped movements and has been associated with mutations of the alpha 4 and beta 2 subunits of the neuronal nicotinic acetylcholine receptor. We performed a clinical and molecular genetic study of a large pedigree segregating sleep-related epilepsy in which seizures are associated with fear sensation, tongue movements, and nocturnal wandering, closely resembling nightmares and sleep walking. We identified a new genetic locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.3. By sequencing the positional candidate neuronal cholinergic receptor alpha 2 subunit gene (CHRNA2), we detected a heterozygous missense mutation, I279N, in the first transmembrane domain that is crucial for receptor function. Whole-cell recordings of transiently transfected HEK293 cells expressing either the mutant or the wild-type receptor showed that the new CHRNA2 mutation markedly increases the receptor sensitivity to acetylcholine, therefore indicating that the nicotinic alpha 2 subunit alteration is the underlying cause. CHRNA2 is the third neuronal cholinergic receptor gene to be associated with familial sleep-related epilepsies. Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior
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