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)

Calcium current, Ica, was studied in isolated nerve cell bodies of Helix aspersa after suppression of Na+ and K+ currents. The suction pipette method described in the preceding paper was used. Ica rises to a peak value and then subsides exponentially and has a null potential of 150 mV or more and a relationship with [Ca2+]o that is hyperbolic over a small range of [Ca2+]o's. When [Ca2+]i is increased, Ica is reduced disproportionately, but the effect is not hyperbolic. Ica is blocked by extracellular Ni2+, La3+, Cd2+, and Co2+ and is greater when Ba2+ and Sr2+ carry the current. Saturation and blockage are described by a Langmuir adsorption relationship similar to that found in Balanus. Thus, the calcium conductance probably contains a site which binds the ions referred to. The site also appears to be voltage-dependent. Activation and inactivation of Ica are described by first order kinetics, and there is evidence that the processes are coupled. For example, inactivation is delayed slightly in its onset and tau inactivation depends upon the method of study. However, the currents are described equally well by either a noncoupled Hodgkin-Huxley mh scheme or a coupled reaction. Facilitation of Ica by prepulses was not observed. For times up to 50 ms, currents even at small depolarizations were accounted for by suitable adjustment of the activation and inactivation rate constants.
 ...
PMID:The calcium current of Helix neuron. 66 Jan 60

1. Whole-cell K+ currents contributing to the resting membrane potential and repolarization of the action potential were studied in voltage-clamped parasympathetic neurones dissociated from neonatal rat intracardiac ganglia and maintained in tissue culture. 2. Rat intracardiac neurones had a mean resting membrane potential of -52 mV and mean input resistance of 850 M omega. The current-voltage relationship recorded during slow voltage ramps indicated the presence of both leakage and voltage-dependent currents. The contribution of Na+, K+ and Cl- to the resting membrane potential was examined and relative ionic permeabilities PNa/PK = 0.12 and PCl/PK < 0.001 were calculated using the Goldman-Hodgkin-Katz voltage equation. Bath application of the potassium channel blockers, tetraethylammonium ions (TEA; 1 mM) or Ba2+ (1 mM) depolarized the neurone by approximately 10 mV. Inhibition of the Na(+)-K+ pump by exposure to K(+)-free medium or by the addition of 0.1 mM ouabain to the bath solution depolarized the neurone by 3-5 mV. 3. In most neurones, depolarizing current pulses (0.5-1 s duration) elicited a single action potential of 85-100 mV, followed by an after-hyperpolarization of 200-500 ms. In 10-15% of the neurones, sustained current injection produced repetitive firing at maximal frequency of 5-8 Hz. 4. Tetrodotoxin (TTX; 300 nM) reduced, but failed to abolish, the action potential. The magnitude and duration of the TTX-insensitive action potential increased with the extracellular Ca2+ concentration, and was inhibited by bath application of 0.1 mM Cd2+. The repolarization rate of the TTX-insensitive action potential was reduced, and after-hyperpolarization was replaced by after-depolarization upon substitution of internal K+ by Cs+. The after-hyperpolarization of the action potential was reduced by bath application of Cd2+ (0.1 mM) and abolished by the addition of Cd2+ and TEA (10 mM). 5. Depolarization-activated outward K+ currents were isolated by adding 300 nM TTX and 0.1 mM Cd2+ to the external solution. The outward currents evoked by step depolarizations increased to a steady-state plateau which was maintained for > 5 s. The instantaneous current-voltage relationship, examined under varying external K+ concentrations, was linear, and the reversal (zero current) potential shifted in accordance with that predicted by the Nernst equation for a K(+)-selective electrode. The shift in reversal potential of the tail currents as a function of the extracellular K+ concentration gave a relative permeability, PNa/PK = 0.02 for the delayed outward K+ channel(s).(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Resting membrane potential and potassium currents in cultured parasympathetic neurones from rat intracardiac ganglia. 128 80

1. Low voltage-activated (LVA) Ca2+ current in clonal (GH3) pituitary cells was studied with the use of the whole-cell recording technique. The use of internal fluoride to facilitate the rundown of high voltage-activated (HVA) Ca2+ current allowed the study of LVA current in virtual isolation. 2. In 10 mM [Ca2+]o, detectable LVA current begins to appear at about -50 mV, with half-maximal activation occurring at -33 mV. The time course of activation was best described by a Hodgkin-Huxley expression with n = 3, suggesting that at least three closed states must be traversed before channel opening. 3. Deactivation was found to vary exponentially with membrane potential between -60 and -160 mV, indicating that channel closing is rate-limited by a single, voltage-dependent transition. 4. Onset and removal of inactivation between -40 and -130 mV were best described by the sum of two exponentials. Between -80 and -130 mV, both components of removal of inactivation showed little voltage dependence, with time constants of approximately 200-300 ms and 1-2 s. At membrane potentials above -40 mV, a single component of inactivation onset was detected. This component was voltage independent between -20 and +20 mV (tau = 22 ms). Thus inactivation of LVA current is best described by multiple, voltage-in-dependent processes. 5. Significant inactivation of LVA current occurred at -65 mV without detectable macroscopic current. This suggests that inactivation is not strictly coupled to channel opening. 6. Peak LVA current increased with increasing [Ca2+]o, with saturation approximately 50 mM. The Ca(2+)-dependence of peak LVA current was reasonably well described by a single-site binding isotherm with half-maximal LVA current at approximately 7 mM. 7. LVA current in GH3 cells was largely resistant to blockade by Ni2+. The relative potency of inorganic cations in blocking GH3 LVA current was (concentrations which produced 50% block): La3+ (2.4 microM) greater than Cd2+ (188 microM) greater than Ni2+ (777 microM). 8. Several organic agents, including putative LVA blockers, HVA current blockers and various anesthetic agents, were tested for their ability to block LVA current. The concentrations that produced 50% block are as follows: nifedipine (approximately 50 microM), D600 (51 microM), diltiazem (131 microM), octanol (244 microM), pentobarbital (985 microM), methoxyflurane (1.41 mM), and amiloride (1.55 mM). Phenytoin and ethosuximide produced 36 and 10% block at 100 microM and 2.5 mM, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Kinetic and pharmacological properties of low voltage-activated Ca2+ current in rat clonal (GH3) pituitary cells. 132 46

The mechanism of Cd2+ block of Ca2+ currents (ICa) was explored in squid neurons using whole-cell patch clamp. Control currents activated sigmoidally, more rapidly at more positive potentials, and did not inactivate significantly. External Cd2+ up to 250 microM reduced ICa reversibly. For small depolarizations, the current for a step of 10 ms increased to a maintained value, resembling the control; but for Vm greater than 0 mV, the increase was followed by a decrease, as Cd2+ block became greater. Final block was greater for larger depolarizations. At 0 mV the half-blocking concentration was 125 microM. Tail currents, measured as channels close, had an initial "hook" when recorded in Cd2+: currents increased transiently, then decreased. This suggests that Cd2+ escapes from some channels, which then conduct briefly before closing. Analysis of tail currents shows that Cd2+ does not slow channel closing. The data can be explained if Cd2+ is a permeant blocker of Ca2+ channels and if channels can close when occupied by Cd2+. Cd2+ permeates the channels, but binds transiently to a site in the pore, obstructing the passage of other ions (e.g., Ca2+). Dwell time depends on the transmembrane potential, becoming shorter for more negative internal potentials. A five-state model was used to simulate the steady-state and kinetic features. It combines a Hodgkin-Huxley type m2 gating scheme and a one-site Woodhull ionic blockage model for a permeant blocker and includes a closed blocked state. To fit the data, the binding site for Cd2+ had to be near the outer end of the pore, with a well depth of -12.2 RT, and with a barrier at each end of the pore. The model predicts that the Cd2+ entry rate is nearly voltage independent, but the exit rate is steeply voltage dependent (e-fold/17 mV). Analysis further suggests that the channel closes at a normal rate with Cd2+ in the pore.
 ...
PMID:Cadmium block of squid calcium currents. Macroscopic data and a kinetic model. 166 61

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.
 ...
PMID:[2 calcium currents in the somatic membrane of neurons of Helix pomatia]. 241 33

A quantitative description of the time-dependent and voltage-sensitive outward currents in heart has been hampered by the complications inherent to the multicellular preparations previously used. We have used the whole-cell patch-clamp technique to record the delayed outward K+ current, IK, in single cells dissociated from frog atrium. Na+ currents were blocked with tetrodotoxin and Ca2+ currents with Mn2+ or Cd2+. After depolarizations from -50 mV to potentials positive to -30 mV, a time-dependent outward current was observed. This current has been characterized according to its steady state activation, kinetics, and ion transfer function. The current is well described as a single Hodgkin-Huxley conductance. The deactivation of the current is a single exponential. Activation of the current is sigmoid and is fitted well by raising the activation variable to the second power. The reversal potential of IK is near EK and shifts by 57 mV/10-fold change in [K+]o. This suggests that the current is carried selectively by K ions. The threshold for activation is near -30 mV. IK is maximally activated positive to +20 mV and shows no inactivation. The fully activated current-voltage relationship is linear between -110 and +50 mV. Neither Ba2+ (250 microM) nor Cd2+ (100 microM) affects IK.
 ...
PMID:A time-dependent and voltage-sensitive K+ current in single cells from frog atrium. 243 57

1. Ganglion cells were dissociated from the enzyme-treated rat retina, identified with specific fluorescent labels, and maintained in vitro. Electrophysiological properties of solitary retinal ganglion cells were investigated with both conventional intracellular and patch-clamp recordings. Although comparable results were obtained for most measurements some important differences were noted. 2. The input resistance of solitary retinal ganglion cells was considerably higher when measured with 'giga-seal' suction pipettes than with conventional intracellular electrodes. Under current-clamp conditions with both intracellular and patch pipettes, these central mammalian neurones maintained resting potentials of about -60 mV and displayed action potentials followed by an after-hyperpolarization in response to small depolarizations. The membrane currents during this activity, analysed under voltage clamp with patch pipettes, consisted of five components: Na+ current (INa), Ca2+ current (ICa), and currents with properties similar to the delayed outward, the transient (A-type), and the Ca2+-activated K+ currents (IK, IA and IK(Ca), respectively). 3. Ionic substitution, pharmacological agents, and voltage-clamp experiments revealed that the regenerative currents were carried by both Na+ and Ca2+. 100 nM-1 microM-tetradotoxin (TTX) reversibly blocked the fast spikes carried by the presumptive INa, which under voltage-clamp analysis had classical Hodgkin-Huxley-type activation and inactivation. 4. Single-channel recordings of the Na+ current (iNa) permitted comparison of these 'microscopic' events with the 'macroscopic' whole-cell current (INa). The inactivation time constant (tau h) fitted to the averaged single-channel recordings of iNa in outside-out patches was slower than the tau h obtained during whole-cell recordings of INa. 5. In the presence of 1-40 microM-TTX and 20 mM-TEA, slow action potentials appeared in intracellular recordings and were probably mediated by Ca2+. The potentials were abrogated by 3 mM-Co2+ or 200 microM-Cd2+; conversely, increasing the extracellular Ca2+ concentration from 2.5 to 10-25 mM or substitution of 1 mM-Ba2+ for 2.5 mM-Ca2+ enhanced their amplitude. ICa was measured directly in whole-cell recordings with patch pipettes after blocking INa with extracellular 1 microM-TTX and K+ currents with intracellular 120-mM Cs+ and 20 mM-TEA. 6. During whole-cell recordings with patch electrodes, extracellular 20 mM-TEA suppressed IK and, to a lesser extent, IA. Extracellular 5 mM-4-AP or a pre-pulse of the membrane potential to -40 mV prior to stronger depolarization completely blocked IA.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Voltage-dependent conductances of solitary ganglion cells dissociated from the rat retina. 244 69

1. Monovalent cation selectivity and divalent cation sensitivity of the tetrodotoxin (TTX)-resistant Na+ current in dissociated adult rat nodose ganglion neurones were investigated using the whole-cell patch-clamp technique. 2. The TTX-resistant Na+ current was isolated using ion substitution and pharmacological agents. Under these conditions, the current reversal potential shifted 52 mV per tenfold change in external [Na+]. 3. Inorganic and organic monovalent cation permeability ratios (Px/PNa) were determined from changes in reversal potential and the Goldman-Hodgkin-Katz equation. The Px/PNa values determined by the former method were HONH3+, 1.38; Li+, 1.00; H2NNH3+, 0.66; NH4+, 0.28; CH3NH3+, less than 0.13; K+, less than 0.13; Rb+, less than 0.12; Cs+, less than 0.10; (CH3)4N+, less than 0.10. The values determined by either method agreed within 10%. 4. The effects of Cd2+, Co2+, Mn2+ and Ni2+ on the TTX-resistant Na+ current were analysed from peak-conductance values. These ions shifted the activation of the current to more positive potentials and decreased the maximal conductance. At 3 mM concentrations, Cd2+, Ni2+, Co2+ and Mn2+ decreased the maximal conductance 64.6, 50.7, 25.0 and 20.3%, respectively. 5. The results indicate that: (a) the monovalent cation selectivity of the TTX-resistant Na+ current is similar to that of the TTX-sensitive Na+ current in other tissues; and (b) the TTX-resistant Na+ current is less sensitive to divalent cations than the Ca2+ current in these neurones. These observations suggest that the structure determining the monovalent cation permeability of the TTX-resistant Na+ current is similar to that of the TTX-sensitive Na+ current in other tissues, and that the channels carrying the TTX-resistant Na+ current are distinct from those responsible for the Ca2+ current.
 ...
PMID:Tetrodotoxin-resistant sodium current of rat nodose neurones: monovalent cation selectivity and divalent cation block. 244 74

1. Neurones were isolated from the CA1 region of the guinea-pig hippocampus and subjected to the whole-cell mode of voltage clamping, to determine the kinetics of voltage-gated Ca2+ channel activation. 2. Isolated neurones had an abbreviated morphology, having lost most of the distal dendritic tree during the isolation procedure. The electrical compactness of the cells facilitates voltage clamp analysis. 3. Block of sodium and potassium currents revealed a persistent current activated on depolarization above -40 mV, which inactivated slowly when the intracellular medium contained EGTA. The current was blocked by Co2+ and Cd2+, augmented by increases in Ca2+ and could be carried by Ba2+, suggesting that the current is borne by Ca2+. 4. Steady-state activation of the Ca2+ current was found to be well described by the Boltzman equation raised to the second power. 5. The open channel's current-voltage (I-V) relationship rectified in the inward direction and was consistent with the constant-field equation. 6. The kinetics of Ca2+ current onset followed m2 kinetics throughout the range of its activation. Tail current kinetics were in accord with this model. A detailed Hodgkin-Huxley model was derived, defining the activation of this current. 7. The kinetics of the currents observed in this regionally and morphologically defined class of neurones were consistent with the existence of a single kinetic class of channels.
 ...
PMID:Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. 245 32

1. Membrane conductance parameters for the rat sympathetic neurone in vitro at 37 degrees C have been determined by two-electrode voltage-clamp analysis. The activation kinetics of two ionic currents, IA and IK(V), has been considered. Data for both currents are expressed in terms of Hodgkin-Huxley equations. 2. The isolated IA developed following third-order kinetics. The activation time constant, tau a, was estimated from the current time-to-peak and, for V less than or equal to -40 mV, from the IA tail current analysis upon membrane repolarization to various potentials. The maximum tau a occurred at -55 mV and varied from 0.26 to 0.82 ms in the range of potentials between -100 and +10 mV. The steady-state value of the variable a, corrected for inactivation, was evaluated in the voltage range from -60 to 0 mV; 14.4 mV are required to change a infinity e-fold. Steady-state gA was voltage dependent, increasing with depolarization to a maximum of 1.40 microS at +10 mV. 3. IK(V) was similarly analysed in isolation. The current proved to develop as a first-order process. tau n was determined by fitting a single exponential to the IK(V) rising phase and to the tail currents at the end of short depolarizing pulses. The bell-shaped voltage dependence of tau n exhibited a maximum (25.5 ms) at -30 mV, becoming minimal (1.8 ms) at -80 and +20 mV. The n infinity curve was obtained (n infinity = 0.5 at -6.54 mV; k = 8.91 mV). The mean maximum conductance, gK(V), was 0.33 microS per neurone at +10 mV. 4. Single spikes have been elicited by brief current pulses at membrane potentials from -40 to -100 mV under two-electrode current-clamp conditions in normal saline and in the presence of blockers of the ICa-IK(Ca) (Cd2+) and/or IK(V) (TEA, tetraethylammonium) systems. Spike repolarization was affected by the suppression of either current in the depolarized neurone, but was insensitive to both treatments when the spike arose from holding levels negative to -75 to -80 mV, indicating that at these membrane potentials the IA current mainly, if not exclusively, contributes to the action potential falling phase. 5. The basic features of the sympathetic neurone action potential were reconstructed by simulations based on present and previous voltage-clamp characterization of the IA, IK(V) and INa conductances.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The interactions between potassium and sodium currents in generating action potentials in the rat sympathetic neurone. 245 94


1 2 3 Next >>