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Query: UMLS:C0019829 (Hodgkin's disease)
30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kinetics of calcium binding by photoreceptor membranes of cattle retina in concentration Ca2+ 0.5 and 1.0.10(-5) M in 5 mM tris-HCl buffer, pH 7.4 at 37 degrees C has been studied. Such kinetics is of oscillating nature. Analysis of calcium binding process curves by photoreceptor membranes allow to conclude, that crystalline areas of rhodopsin (receptor domains) can be formed in the structure of photoreceptor membranes. Conformation states and structure of rhodopsin molecules Ca-binding sites in receptor domains depend on the presence of Ca2+ in the medium. The structure of rhodopsin molecules Ca-binding sites in receptor domain formed in the presence of Ca2+ in the medium was proposed. According to the Hodgkin and Huxley conception concerning the properties of Na(+)- and K(+)-channels, the receptor domain with such a structure of rhodopsin molecules Ca-binding sites can represent the conjugate system of Na(+)- and K(+)-channels. Molecular mechanisms of photoreceptor and nerve cells excitation was also proposed.
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PMID:[A molecular model of cooperative binding of Ca2+ with rhodopsin molecules in photoreceptor membranes]. 179 12

1. Voltage- and time-dependent outward currents were recorded from relaxed enzymatically isolated smooth muscle cells from the rabbit left descending coronary artery using a single pipette voltage clamp technique. The calcium-activated potassium current was blocked by inclusion of EGTA in the pipette solution and CdCl2 in the extracellular bath. 2. Outward currents were elicited with depolarizing voltage steps to potentials positive to -20 mV. Long (5 s) voltage steps revealed slow inactivation of the current with a time constant of nearly 3 s at +60 mV. Potassium was identified as the predominant charge carrier by reversal potential measurements in potassium substitution experiments. 3. The results of kinetic analyses compared favourably with the Hodgkin-Huxley model for a delayed rectifier with some deviations. The sigmoid current onset was best fitted by raising the activation variable (n) to the second power. Deactivation tail currents were consistently found to be comprised of two exponential components. The kinetics of activation and deactivation were strongly voltage-dependent from -80 to +60 mV. 4. Envelope of tails experiments showed that the scaled tail current amplitudes followed the kinetic behaviour of current activation. The contribution of each of the two exponential tail components was also measured in these experiments. They did not reveal kinetically separable currents, nor were they differentially altered by 4-aminopyridine (4-AP), tetraethylammonium (TEA), or elevated [K+]o. 5. The steady-state voltage-dependence curves for both activation and inactivation were well fitted by a Boltzmann distribution with V1/2 = -5.60 mV and k = -8.66 mV for n infinity act and V1/2 = -24.20 mV and k = 5.16 mV for n infinity act. Super-imposition of the two curves revealed a 'window' of voltage where channels are available for activation without completely inactivating. 6. Neither of the commonly used potassium channel blockers, TEA or 4-AP, were particularly effective blockers of IK, reducing current by only 50-70% at an extracellular concentration of 10 mM. TEA block was mildly voltage-dependent and was more effective in reducing current towards the end of a 500 ms depolarization. 4-AP, on the other hand, demonstrated considerable voltage-dependence and preferentially reduced early currents. 7. Outward currents recorded from guinea-pig and human coronary artery myocytes under the same conditions as in the rabbit cell experiments displayed similar characteristics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A voltage-dependent potassium current in rabbit coronary artery smooth muscle cells. 191 87

1. The patch-clamp method was applied to the study of ionic currents activated by depolarization of undifferentiated IMR-32 human neuroblastoma cells. Whole-cell sodium and potassium currents and single potassium ion channel currents from cell-attached patches were investigated. 2. Cells had a mean resting potential of -38 mV and mean input resistance of 1.6 G omega. Single action potentials were evoked under current clamp during the injection of depolarizing currents. 3. A voltage-dependent inward sodium current was observed which reversed at +44 mV. A Boltzmann fit to the activation curve gave a half-maximal activation voltage of -41.6 mV and a 'slope' of 3.9 mV. The steady-state inactivation curve had a half-maximal inactivation voltage of -81 mV and a 'slope' of 9.7 mV. 4. The time-dependent activation and inactivation of the current displayed classical Hodgkin-Huxley kinetics. Values for the time constants tau m and tau h of 0.16 and 0.63 ms were calculated for a voltage jump from -80 to -10 mV; tau m and tau h decreased as the step potential was changed from -30 to +20 mV. 5. Outward currents were activated in bathing solutions substantially free of anions and could thus be attributed to potassium ions. The tail current reversed in direction on repolarization to -60 mV when the potassium concentration in the bathing solution was increased from 6 to 30 mM. When the bathing solution contained 145 mM-potassium, and the patch pipette, 95 mM, a depolarization to -10 mV from a holding potential of -60 mV evoked an inward current. 6. Outward currents were examined by using voltage pulses which depolarized the cell to -20 mV, or more positive values, from a holding potential of -80 mV and by pulses which depolarized the cell to 0 mV, or to positive values, from a holding potential of -30 mV. A Boltzmann fit of typical activation data gave a half-maximal activation voltage of 17 mV and a 'slope' of 14 mV. 7. The time course of the rising phase of the current was described by a function of the form A(1-exp[-(t-delta t)/tau]), where delta t varied between 1 and 4 ms and tau varied between 4 and 27 ms, decreasing with increasing depolarization. There was no evidence for a fast transient component. 8. The amplitude of outward currents was reduced by extracellular calcium ions, cobalt ions, tetraethylammonium and 4-aminopyridine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the sodium and potassium currents of a human neuroblastoma cell line. 202 15

The origin of the action potential in neurones has yet to be answered satisfactorily for most cells. We present here a five-conductance model of the somatic membrane of the mature and intact sympathetic neurone studied in situ in the isolated rat superior cervical ganglion under two-electrode voltage-clamp conditions. The neural membrane hosts five separate types of voltage-dependent ionic conductances, which have been isolated at 37 degrees C by using simple manipulations such as conditioning-test protocols and external ionic pharmacological treatments. The total current could be separated into two distinct inward components: (1) the sodium current, INa, and (2) the calcium current, ICa; and three outward components: (1) the delayed rectifier, IKV, (2) the transient IA, and (3) the calcium-dependent IKCa. Each current has been kinetically characterized in the framework of the Hodgkin-Huxley scheme used for the squid giant axon. Continuous mathematical functions are now available for the activation and inactivation (where present) gating mechanisms of each current which, together with the maximum conductance values measured in the experiments, allow for a satisfactory reconstruction of the individual current tracings over a wide range of membrane voltage. The results obtained are integrated in a full mathematical model which, by describing the electrical behaviour of the neurone under current-clamp conditions, leads to a quantitative understanding of the physiological firing pattern. While, as expected, the fast inward current carried by Na+ contributes to the depolarizing phase of the action potential, the spike falling phase is more complex than previous explanations. IKCa, with a minor contribution from IKV, repolarizes the neurone only under conditions of low cell internal negativity. Their role becomes less pronounced in the voltage range negative to -60 mV, where membrane repolarization allows IA to deinactivate. In the spike arising from these voltage levels the membrane repolarization is mainly sustained by IA, which proves to be the only current sufficiently fast and large enough to recharge the membrane capacitor at the speed observed during activity. Different modes of firing coexist in the same neurone and the switching from one to another is fast and governed by the membrane potential level, which makes the selection between the different voltage-dependent channel systems. The neurone thus seems to be prepared to operate within a wide voltage range; the results presented indicate the basic factors underlying the different discrete behaviours.
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PMID:A five-conductance model of the action potential in the rat sympathetic neurone. 205 76

1. Intracellular recordings were made from locus coeruleus (LC) neurones in a totally submerged brain slice preparation from adult rats. The effect of gamma-aminobutyric acid (GABA) on LC neurones was studied under current-clamp and voltage-clamp conditions. GABA caused inhibition of spontaneous firing and a large conductance increase in LC neurones. These effects could be accompanied by depolarization, hyperpolarization or little change in membrane potential depending on the presence or absence of Cl- in the recording microelectrode. 2. The reversal potential for GABA-induced changes in membrane potential (EGABA) was -71.3 +/- 1.1 mV (S.E.M., n = 21) in cells impaled with potassium acetate electrodes and -47.5 +/- 1.4 mV (S.E.M., n = 15) in cells impaled with KCl electrodes. When the external Cl- concentration was reduced EGABA was shifted in the depolarizing direction by 51.5 mV per tenfold change in external Cl- which is close to the shift predicted by the Nernst equation for a selective increase in CL- conductance. 3. GABA effects on LC neurones result from a direct action since they persist in low-Ca2+ and high-Mg2+ media which block synaptic transmission. 4. The effects of GABA were concentration dependent and antagonized by bicuculline (10 microM) and bicuculline methiodide (80-100 microM) indicating that they were mediated predominantly by an action on GABAA receptors. In the presence of bicuculline, EGABA was shifted towards the K+ equilibrium potential which indicated a residual bicuculline-resistant action at GABAB receptors. 5. GABA-induced responses were membrane potential dependent. GABA conductance was observed to decrease with membrane hyperpolarization in a linear manner. GABA-induced current showed outward rectification. In the voltage range studied (rest to -110 mV) the extent of this rectification was predicted by the Goldman-Hodgkin-Katz equation, suggesting that it was due to the unequal distribution of Cl- across the membrane. In addition, the time constant of decay of GABA current was decreased by membrane hyperpolarization; this could be due to a voltage-dependent change in receptor or channel kinetics. 6. These data suggest that the primary action of GABA on LC neurones is to increase Cl- conductance by activation of bicuculline-sensitive GABAA receptors. Due to the voltage dependence of GABA responses, GABA will exert a stronger inhibitory effect on LC neurones at depolarized than at hyperpolarized membrane potentials. This could serve as a negative feedback mechanism to control excitability of these neurones.
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PMID:gamma-Aminobutyric acid responses in rat locus coeruleus neurones in vitro: a current-clamp and voltage-clamp study. 234 90

We present a model for a conditional bursting neuron consisting of five conductances: Hodgkin-Huxley type time- and voltage-dependent Na+ and K+ conductances, a calcium activated voltage-dependent K+ conductance, a calcium-inhibited time- and voltage-dependent Ca++ conductance, and a leakage Cl- conductance. With an initial set of parameters (version S), the model shows a hyperpolarized steady-state membrane potential at which the neuron is silent. Increasing gNa and decreasing gCl, where gi is the maximal conductance for species i, produces bursts of action potentials (Burster N). Alternatively, an increase in gCa produces a different bursting state (Burster C). The two bursting states differ in the periods and amplitudes of their bursting pacemaker potentials. They show different steady-state I-V curves under simulated voltage-clamp conditions; in simulations that mimic a steady-state I-V curve taken under experimental conditions only Burster N shows a negative slope resistance region. Model C continues to burst in the presence of TTX, while bursting in Model N is suppressed in TTX. Hybrid models show a smooth transition between the two states.
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PMID:Multiple modes of a conditional neural oscillator. 235 77

1. Electrical and pharmacologic properties of ATP-induced current in outer hair cells isolated from guinea pig cochlea were investigated in the whole-cell recording mode by the use of a conventional patch-clamp technique. 2. Under current-clamp conditions, rapid application of ATP depolarized the outer hair cells resulting in an increase in conductance. The ATP-induced response did not show any desensitization during a continuous application. 3. At a holding potential of -70 mV, the ATP-induced inward current increased in a sigmoidal fashion over the concentration range between 3 microM and 1 mM. The half-maximum concentration (EC50) was 12 microM and the Hill coefficient was 0.93. 4. The ATP-induced current had a reversal potential near 6 mV, which was close to the theoretical value (1 mV) calculated from the Goldman-Hodgkin-Katz equation for permeable intra- and extracellular cations. 5. In the current-voltage (I-V) relationship for the ATP response, a slight inward-going rectification was observed at more positive potentials than the reversal potential. 6. The substitution of extracellular Na+ by equimolar choline+ shifted the reversal potential of the ATP-induced current to more negative values. The substitution of Cs+ in the internal solution by N-methyl-D-glucamine+ (NMG+) shifted it in the positive direction. The reversal potential of ATP-induced current was also shifted to positive values with increasing extracellular Ca2+ concentration. A decrease of intracellular Cl- by gluconate- did not affect the reversal potential, thereby indicating that the ATP-induced current is carried through a large cation channel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ATP-induced current in isolated outer hair cells of guinea pig cochlea. 235 62

Two different calcium currents were revealed in the somatic membrane of Helix pomatia neurons. In addition to the main current described in literature, depolarizing the membrane from the holding potential level (-120 divided by -100 mV) an additional calcium current was observed. It was activated at depolarizations to -80 divided by -40 mV. Contrary to the main calcium current it did not deteriorate during intracellular perfusion by solutions containing fluoride. Time-dependence of this current could be described in the framework of the Hodgkin-Huxley model with time constants for activation and inactivation equal to tau m = 6-8 ms and tau h = 300-600 ms, respectively. The amplitude of this current increased with increase of extracellular Ca2+ concentration and decreased after addition of Co2+, Ni2+, Cd2+, nifedipine and verapamil. Dissociation constants of these substances with corresponding channels determined for the maximum of current-voltage relationship were 2 (Ca2+), 3 (Co2+), 0.06 (nifedipine) and 0.2 mmol/l (verapamil). Properties of the fluoride-insensitive calcium current and data obtained for other calcium channels are compared. Its possible functional role is also discussed.
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PMID:[2 calcium currents in the somatic membrane of neurons of Helix pomatia]. 241 33

Spontaneously active single cells have been obtained from the sinus venosus region of the bull-frog, Rana catesbeiana, using an enzymic dispersion procedure involving serial applications of trypsin, collagenase and elastase in nominally 0 Ca2+ Ringer solution. These cells have normal action potentials and fire spontaneously at a rate very similar to the intact sinus venosus. A single suction micro-electrode technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981; Hume & Giles, 1983) has been used to record the spontaneous diastolic depolarizations or pace-maker activity as well as the regenerative action potentials in these cells. This electrophysiological activity is completely insensitive to tetrodotoxin (TTX; 3 X 10(-6) M) and is very similar to that recorded from an in vitro sinus venosus preparation. The present experiments were aimed at identifying the transmembrane potassium currents, and analysing their role(s) in the development of the pace-maker potential and the repolarization of the action potential. Depolarizing voltage-clamp steps from the normal maximum diastolic potential (-75 mV) elicit a time- and voltage-dependent activation of an outward current. The reversal potential of this current in normal Ringer solution [( K+]0 2.5 mM) is near -95 mV; and it shifts by 51 mV per tenfold increase in [K+]0, which strongly suggests that this current is carried by K+. We therefore labelled it IK. The reversal potential of IK did not shift in the positive direction following very long (20 s) depolarizing clamp steps to +20 mV, indicating that 'extracellular' accumulation of [K+]0 does not produce any significant artifacts. The fully activated instantaneous current-voltage (I-V) relationship for IK is approximately linear over the range of potentials -130 to -30 mV. Thus, the ion transfer mechanism of IK may be described as a simple ohmic conductance in this range of potentials. Positive relative to -30 mV, however, the I-V exhibits significant inward rectification. A Hodgkin-Huxley analysis of the kinetics of IK, including a demonstration that the envelope of tails quantitatively matches the time course of the onset of IK during a prolonged depolarizing clamp step has been completed. The steady-state activation variable (n infinity) of IK spans the voltage range approximately -40 to +10 mV. It is well-fitted by a Boltzmann distribution function with half-activation at -20 mV. The time course of decay of IK is a single exponential. However, the activation or onset of IK shows clear sigmoidicity in the range of potentials from the activation threshold (-40 mV) to 0 mV.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Voltage clamp of bull-frog cardiac pace-maker cells: a quantitative analysis of potassium currents. 241 14

A physical system is derived which has properties which are the same as those computed for the potassium conductance system in the squid axon with the Hodgkin-Huxley equations. The system describes a molecule with five ionization states which, on hyperpolarization, are stripped of singly charged ions (H+?), and doubly charged ions (Ca++?). The dependence of potassium conductance on pH and on the calcium substrate concentration is predicted by the physical system. The effect of enzyme or allosteric interactions in producing inactivation or blocking of conductance is discussed. To consider these effects, the isomorphism is augmented to an 8-state system. This 8-state system encompasses the properties of both the potassium and, with different parameters, the sodium conductance. It is thus general enough to describe all the HH equations in the potential region used for the determination of the HH parameters, namely, -30 to 110 mV transmembrane potential.
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PMID:Isomorphism on a physical system of the Hodgkin-Huxley equations for potassium conductance. 241 63


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