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

Calcium currents (ICa) were recorded in frog skeletal muscle fibres using the three-micro-electrode voltage-clamp technique. The sartorius muscle was bathed in TEA methanesulphonate saline with 350 mM-sucrose. 5 mM-3,4-diaminopyridine was added to the saline to minimize K+ currents. The I-V relationship for peak Ca2+ currents showed that ICa was detected at -40 mV and reached a maximum value at ca. -10 mV. No net inward current was recorded at potentials positive to ca. +40 mV. Remaining K+ currents (IK) were recorded by replacing 10 mM-Ca2+ with 5.5 mM-Co2+. They were not noticeably time-dependent up to +20 mV and would tend to diminish the amplitude of ICa without greatly affecting its time course. ICa tail currents could be separated from non-linear capacity currents. Tail currents were measured 5 msec after repolarization and extrapolated to the end of the pulse. ICa tail-current amplitudes at EK were measured with pulses of different durations. The envelope of tail-current amplitudes declined with a time course similar or identical to that of inward current during a maintained depolarization. Consequently, the decline of inward current cannot be explained by an increase of outward IK with time. ICa inactivated with 9 sec prepulses which did not elicit detectable ICa. The fitted h infinity curve had a mid point of -33.0 mV and a steepness of 6.3 mV. ICa between -30 mV and +20 mV could be described adequately using the Hodgkin-Huxley m3h relationship. The fitted m infinity curve had a mid point of -35.2 mV and a steepness of 9.9 mV. The limiting Ca2+ permeability PCa was 1.4 +/- 0.4 X 10(-4) cm/sec.
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PMID:Kinetic properties of calcium channels of twitch muscle fibres of the frog. 630 34

The kinetics of the TEA and 4-AP sensitive K+ current (IK) in the slowly adapting lobster stretch receptor neurone were investigated in sub- and near-threshold voltage regions using electrophysiological and pharmacological techniques. In dynamic conditions IK was found to display both fast and slow reactions. These were attributed to a Hodgkin-Huxley type of K activation, and a slow type of K inactivation, respectively. The slow K inactivation could be shown to be unrelated to K+ flux dependent changes in intra- and pericellular K+ concentrations. Its stationary voltage dependence was however shifted in a depolarizing direction by increasing, and in hyperpolarizing direction by decreasing the extracellular Ca++ concentration. In view of these findings, and of its kinetic properties, the slow K inactivation was classified as a genuine channel gating process. The process of K activation was too fast for a dynamic analysis with the recording technique available. An estimate of its stationary voltage dependence could however be obtained in a voltage range from about -100 to about -40 mV. The experimental observations were utilized in the formulation of a mathematical model describing the kinetic behaviour of IK in the present preparation based on constant field and state transition theories.
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PMID:Kinetics of the TEA and 4-AP sensitive K+ current in the slowly adapting lobster stretch receptor neurone. 631 50

1. When K(+) is removed from both sides of the somal membrane of Limnea neurones, time-dependent, voltage-dependent outward currents are observed at positive potentials. These currents can be carried by Tris(+) and tetraethylammonium (TEA(+)), as well as Cs(+), but the Cs currents are several times larger. The Cs currents are not affected by external or internal TEA, but are strongly reduced by 4-aminopyridine (4-AP) and all Ca blockers tried.2. The presence of these non-specific outward currents and their sensitivity to all treatments that eliminate the Ca currents prevent the complete isolation of Ca currents. The non-specific outward currents are most prominent at large positive potentials and as slow tail currents on stepping back to the holding potential.3. Ca currents are ;washed out' in well perfused cells. Typically the Ca current has decayed to less than one tenth of its original size after (1/2) h of perfusion. This wash-out is specific for the Ca current; Na and K currents persist for several hours.4. Once the Ca current has completely decayed, it is possible to study one type of non-specific current without overlapping inward currents. This current activates between 0 and +30 mV and appears to reverse near 0 mV.5. In spite of the probable presence of slowly activating outward currents, the net inward currents measured show little apparent inactivation. In all the cells studied the inward current evoked at +20 mV has never decayed by more than 50% during a 60 ms pulse. So the true inactivation of these Ca currents must be quite slow, with time constants of the order of 100 ms and larger.6. The activation of the Ca current agrees with m(2) kinetics. The rate of activation is the same for Ba currents as for Ca currents.7. When the membrane potential is stepped back to the holding level (-50 mV), the Ca current turns off quite rapidly with a time constant of about 100 mus (25 degrees C). The time constant for turning off the Ca current is not related to the time constant for turning on the Ca current at the same voltage as expected for m(2) kinetics in the Hodgkin and Huxley model. At -30 mV the tau(m) for turn-on is eight times larger than the tau(m) for turn-off.
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PMID:Calcium currents in internally perfused nerve cell bodies of Limnea stagnalis. 706 29

1. The spread of electrical signals between rods in the salamander retina was examined by passing current into one rod and recording the voltage responses in nearby rods. Rod network behaviour, measured in this way, was simulated from data on rod membrane properties gathered in voltage-clamp experiments on single isolated rods.2. The network voltage responses to square current pulses became smaller, more transient, and had a longer time-to-peak, for rods further away from the site of current injection. Depolarizing currents produced smaller responses than hyperpolarizing currents of the same magnitude.3. Neighbouring rods and cones were coupled less strongly than neighbouring rods.4. The response of the rod network to current injection was unaffected by 2 mm-aspartate(-), which eliminates transmission from receptors to horizontal cells.5. The input resistance of single isolated rods, measured at the resting potential, varied between 100 and 680 MOmega. The lower values were probably due to damage by the micro-electrodes. Electrical coupling was found to be very strong between the rod inner and outer segments.6. A strong ;instantaneous' outward rectification seen in isolated rods at potentials positive to -35 mV was reduced, but not abolished, by 15 mm-TEA.7. In normal solution, isolated rods exhibited a voltage- and time-dependent current, I(A), whose kinetics were approximated by a single first-order gating variable, and whose activation curve spanned the range between -40 and -80 mV. The time constant for the current varied with voltage and was 60-200 msec between -140 and -40 mV.8. A reversal potential for I(A) could not be found between -140 and -40 mV in normal solution, and the fully activated current, I(A), was approximately voltage-independent, with a magnitude of approximately 0.1 nA over this potential range.9. By several criteria, I(A) behaved as a single inward current activated by hyperpolarization. Pharmacological studies suggest, however, that it is the sum of at least two currents with very similar kinetics.10. Most isolated rods exhibited a very slow (tau approximately 3 sec) increase in net outward current on depolarizing beyond -35 mV. The magnitude of this current varied considerably between cells.11. Assuming that the rod network can be approximated by a square lattice of individual rods, resistively coupled together, the voltage-clamp data on isolated rods were used to predict the response of the network to current injection at one cell. The theoretical and observed network behaviour were in good agreement. The resistance coupling neighbouring rods was estimated to be approximately 300 MOmega. The current I(A) plays a major role in determining the behaviour of the rod network.12. The time-dependent current, I(A), is responsible for the peak-plateau wave form of the response to a bright flash. A current similar to I(A) could also account for the negative propagation velocity of the peak of the dim flash response, through the rod network of the turtle, observed by Detwiler, Hodgkin & McNaughton (1978).
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PMID:Behaviour of the rod network in the tiger salamander retina mediated by membrane properties of individual rods. 725 67

Using the two-microelectrode voltage clamp technique in Xenopus laevis oocytes, we estimated Na(+)-K(+)-ATPase activity from the dihydroouabain-sensitive current (IDHO) in the presence of increasing concentrations of tetraethylammonium (TEA+; 0, 5, 10, 20, 40 mM), a well-known blocker of K+ channels. The effects of TEA+ on the total oocyte currents could be separated into two distinct parts: generation of a nonsaturating inward current increasing with negative membrane potentials (VM) and a saturable inhibitory component affecting an outward current easily detectable at positive VM. The nonsaturating component appears to be a barium-sensitive electrodiffusion of TEA+ which can be described by the Goldman-Hodgkin-Katz equation, while the saturating component is consistent with the expected blocking effect of TEA+ on K+ channels. Interestingly, this latter component disappears when the Na(+)-K(+)-ATPase is inhibited by 10 microM DHO. Conversely, TEA+ inhibits a component of IDHO with a KD of 25 +/- 4 mM at +50 mV. As the TEA(+)-sensitive current present in IDHO reversed at -75 mV, we hypothesized that it could come from an inhibition of K+ channels whose activity varies in parallel with the Na(+)-K(+)-ATPase activity. Supporting this hypothesis, the inward portion of this TEA(+)-sensitive current can be completely abolished by the addition of 1 mM Ba2+ to the bath. This study suggests that, in X. laevis oocytes, a close link exists between the Na-K-ATPase activity and TEA(+)-sensitive K+ currents and indicates that, in the absence of effective K+ channel inhibitors, IDHO does not exclusively represent the Na(+)-K(+)-ATPase-generated current.
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PMID:Evidence for coupling between Na+ pump activity and TEA-sensitive K+ currents in Xenopus laevis oocytes. 771 86

The electrophysiological properties of HK2 (Kv1.5), a K+ channel cloned from human ventricle, were investigated after stable expression in a mouse Ltk- cell line. Cell lines that expressed HK2 mRNA displayed a current with delayed rectifier properties at 23 degrees C, while sham transfected cell lines showed neither specific HK2 mRNA hybridization nor voltage-activated currents under whole cell conditions. The expression of the HK2 current has been stable for over two years. The dependence of the reversal potential of this current on the external K+ concentration (55 mV/decade) confirmed K+ selectivity, and the tail envelope test was satisfied, indicating expression of a single population of K+ channels. The activation time course was fast and sigmoidal (time constants declined from 10 ms to < 2 ms between 0 and +60 mV). The midpoint and slope factor of the activation curve were Eh = -14 +/- 5 mV and k = 5.9 +/- 0.9 (n = 31), respectively. Slow partial inactivation was observed especially at large depolarizations (20 +/- 2% after 250 ms at +60 mV, n = 32), and was incomplete in 5 s (69 +/- 3%, n = 14). This slow inactivation appeared to be a genuine gating process and not due to K+ accumulation, because it was present regardless of the size of the current and was observed even with 140 mM external K+ concentration. Slow inactivation had a biexponential time course with largely voltage-independent time constants of approximately 240 and 2,700 ms between -10 and +60 mV. The voltage dependence of slow inactivation overlapped with that of activation: Eh = -25 +/- 4 mV and k = 3.7 +/- 0.7 (n = 14). The fully activated current-voltage relationship displayed outward rectification in 4 mM external K+ concentration, but was more linear at higher external K+ concentrations, changes that could be explained in part on the basis of constant field (Goldman-Hodgkin-Katz) rectification. Activation and inactivation kinetics displayed a marked temperature dependence, resulting in faster activation and enhanced inactivation at higher temperature. The current was sensitive to low concentrations of 4-aminopyridine, but relatively insensitive to external TEA and to high concentrations of dendrotoxin. The expressed current did not resemble either the rapid or the slow components of delayed rectification described in guinea pig myocytes. However, this channel has many similarities to the rapidly activating delayed rectifying currents described in adult rat atrial and neonatal canine epicardial myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression. 850 26

1. Hypoxic stimuli depolarize carotid body type I cells causing voltage-gated calcium influx. This study investigates the cause of this membrane depolarization. Isolated type I cells from neonatal (11-16 day) rat carotid bodies were used in the experiments. 2. Tetraethylammonium (TEA; 10 mM), 1 and 5 mM 4-aminopyridine (4-AP) and 20 nM charybdotoxin all failed to evoke a significant rise in [Ca2+]i. Similarly, in perforated patch whole-cell recordings, a combination of 10 mM TEA and 5 mM 4-AP failed to depolarize type I cells. 3. In type I cells voltage clamped at -70 mV, anoxia evoked a small inward current under control conditions, but had no effect in the absence of pipette and extracellular K+. 4. Anoxia decreased resting membrane conductance from 322 to 131 pS. The anoxia-sensitive current (measured using voltage ramps from -100 to -40 mV) had a reversal potential of -89 mV in 4.5 mM Ko+ and -66 mV in 20 mM Ko+, indicating that this current was carried principally by potassium ions. In contrast, 10 mM TEA + 5 mM 4-AP had little effect on the current-voltage relationship of the cells over the same range. 5. This O2-sensitive K+ conductance showed only mild outward rectification over the range -90 to +30 mV, which could be approximated by the Goldman-Hodgkin-Katz current equation. In addition, there was no time-dependent activation or inactivation of membrane currents elicited by voltage steps in the range -100 to -30 mV. 6. The O2-sensitive K+ conductance was inhibited by graded reductions in PO2 to 40 Torr and below, with a K1/2 of about 12 Torr. 7. The data suggest that hypoxia depolarizes type I cells principally through the inhibition of a small voltage-insensitive resting (or background) K+ conductance, and not through the inhibition of voltage-gated TEA and 4-AP-sensitive K+ channels (e.g. maxi-K or KO2 channels), as has been previously suggested.
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PMID:A novel oxygen-sensitive potassium current in rat carotid body type I cells. 905 77

The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current (IK(A)) was completely inactivated at a holding potential of -50 mV. The remaining potassium current resembled the delayed rectifier current (IK(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with IK(A). The conductance-voltage (G-V) curve revealed that G increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at -40 mV ( approximately 11 ms) and smallest at 100 mV ( approximately 1.5 ms). The properties of IK(A) were studied in the presence of 20 mM TEA, to block IK(DR), and from a holding potential of -15 mV, to inactivate both IK(DR) and IK(A). IK(A) was then allowed to recover from inactivation to negative potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest at -130 mV ( approximately 21 ms) and slowest at -90 mV ( approximately 135 ms). Inactivation was voltage independent from -60 to +60 mV with a time constant of approximately 15 ms. At steady state, IK(A) was half inactivated at -90 mV. GK(A) increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from approximately 1.9 ms at -50 mV to 0.7 ms at +60 mV. The properties of IK(A) resembled those of IK(A) found in differentiating cerebellar granule neurons. Most SVZa cells had sodium currents (28/32 cells). However, in current clamp 11 of 12 cells were incapable of generating action potentials from voltages of -30 to -100 mV, suggesting that the available current densities were too low to support excitability.
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PMID:Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain. 991 70

A mathematical model of midbrain dopamine neurons has been developed to understand the mechanisms underlying two types of calcium-dependent firing patterns that these cells exhibit in vitro. The first is the regular, pacemaker-like firing exhibited in a slice preparation, and the second is a burst firing pattern sometimes exhibited in the presence of apamin. Because both types of oscillations are blocked by nifedipine, we have focused on the slow calcium dynamics underlying these firing modes. The underlying oscillations in membrane potential are best observed when action potentials are blocked by the application of TTX. This converts the regular single-spike firing mode to a slow oscillatory potential (SOP) and apamin-induced bursting to a slow square-wave oscillation. We hypothesize that the SOP results from the interplay between the L-type calcium current (I(Ca,L)) and the apamin-sensitive calcium-activated potassium current (I(K,Ca,SK)). We further hypothesize that the square-wave oscillation results from the alternating voltage activation and calcium inactivation of I(Ca,L). Our model consists of two components: a Hodgkin-Huxley-type membrane model and a fluid compartment model. A material balance on Ca(2+) is provided in the cytosolic fluid compartment, whereas calcium concentration is considered constant in the extracellular compartment. Model parameters were determined using both voltage-clamp and calcium-imaging data from the literature. In addition to modeling the SOP and square-wave oscillations in dopaminergic neurons, the model provides reasonable mimicry of the experimentally observed response of SOPs to TEA application and elongation of the plateau duration of the square-wave oscillations in response to calcium chelation.
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PMID:Calcium dynamics underlying pacemaker-like and burst firing oscillations in midbrain dopaminergic neurons: a computational study. 1056 3

The outer sulcus epithelium was recently shown to absorb cations from the lumen of the gerbil cochlea. Patch clamp recordings of excised apical membrane were made to investigate ion channels that participate in this reabsorptive flux. Three types of channel were observed: (i) a nonselective cation (NSC) channel, (ii) a BK (large conductance, maxi K or K(Ca)) channel and (iii) a small K(+) channel which could not be fully characterized. The NSC channel found in excised insideout patch recordings displayed a linear current-voltage (I-V) relationship (27 pS) and was equally conductive for Na(+) and K(+), but not permeable to Cl(-) or N-methyl-d-glucamine. Channel activity required the presence of Ca(2+) at the cytosolic face, but was detected at Ca(2+) concentrations as low as 10(-7) m (open probability (P(o)) = 0.11 +/- 0.03, n = 8). Gadolinium decreased P(o) of the NSC channel from both the external and cytosolic side (IC(50) approximately 0.6 microm). NSC currents were decreased by amiloride (10 microm - 1 mm) and flufenamic acid (0.1 mm). The BK channel was also frequently (38%) observed in excised patches. In symmetrical 150 mm KCl conditions, the I-V relationship was linear with a conductance of 268 pS. The Goldman-Hodgkin-Katz equation for current carried solely by K(+) could be fitted to the I-V relationship in asymmetrical K(+) and Na(+) solutions. The channel was impermeable to Cl(-) and N-methyl-d-glucamine. P(o) of the BK channel increased with depolarization of the membrane potential and with increasing cytosolic Ca(2+). TEA (20 mm), charybdotoxin (100 nm) and Ba(2+) (1 mm) but not amiloride (1 mm) reduced P(o) from the extracellular side. In contrast, external flufenamic acid (100 microm) increased P(o) and this effect was inhibited by charybdotoxin (100 nm). Flufenamic acid inhibited the inward short-circuit current measured by the vibrating probe and caused a transient outward current. We conclude that the NSC channel is Ca(2+) activated, voltage-insensitive and involved in both constitutive K(+) and Na(+) reabsorption from endolymph while the BK channel might participate in the K(+) pathway under stimulated conditions that produce an elevated intracellular Ca(2+) or depolarized membrane potential.
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PMID:Nonselective cation and BK channels in apical membrane of outer sulcus epithelial cells. 1074 60


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