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)

We have used data obtained from measurements of ionic and gating currents to study the process of K+ channel activation in squid giant axons. A marked improvement in the recording of K+ channel gating currents (IKg) was obtained by total replacement of Cl- in the external solution by NO-3, which eliminates approximately 50% of the Na+ channel gating current with no effect on IKg. The midpoint of the steady state charge-voltage (Qrel - V) relationship is approximately 40 mV hyperpolarized to that of the steady state activation (fo - V) curve, which is an indication that the channel has many nonconducting states. Ionic and gating currents have similar time constants for both ON and OFF pulses. This eliminates any Hodgkin-Huxley nx scheme for K+ channel activation. An interrupted pulse paradigm shows that the last step in the activation process is not rate limiting. IKg shows a nonartifactual rising phase, which indicates that the first step is either the slowest step in the activation sequence or is voltage independent. These data are consistent with the following general scheme for K+ channel activation: (formula; see text)
J Gen Physiol 1985 Apr
PMID:Activation of squid axon K+ channels. Ionic and gating current studies. 240 18

The acetylcholine-activated channel of chick myotube was studied using the patch-clamp method. Single channel current amplitudes were measured between -300 and +250 mV in solutions containing the permeant ions Cs+ and guanidine (G+). G+ has a relative permeability, PG/PCs, of 1.6, but carries no more than half the current that Cs+ does, with an equivalent electrochemical driving force. Experiments using G+ revealed an asymmetry of the acetylcholine-activated channel, with G+ being more effective at reducing Cs+ currents when added to the outside than when added to the inside. The block caused by outside, but not inside, G+ was evident for both inward and outward currents. The block caused by outside G+ was voltage dependent, first increasing and then being partially relieved when the driving force was made more negative. Experiments with mixtures of Cs+ and G+ revealed anomalously low magnitudes for reversal potentials, relative to predictions based on the Goldman-Hodgkin-Katz equation. These findings are consistent with a two-well, three-barrier Eyring rate model for ion flow, and demonstrate that a highly permeant ion, guanidine, can block asymmetrically by acting from within the voltage field of the acetylcholine-activated channel.
J Gen Physiol 1986 Nov
PMID:Guanidine block of single channel currents activated by acetylcholine. 243 Oct 99

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.
J Gen Physiol 1986 Dec
PMID:A time-dependent and voltage-sensitive K+ current in single cells from frog atrium. 243 57

Individual myocytes were isolated from bullfrog atrium by enzymatic and mechanical dispersion, and a one-microelectrode voltage clamp was used to record the slow outward K+ currents. In normal [K+]o (2.5 mM), the slow outward current tails reverse between -95 and -100 mV. This finding, and the observed 51-mV shift of Erev/10-fold change in [K+]o, strongly suggest that the "delayed rectifier" in bullfrog atrial cells is a K+ current. This current, IK, plays an important role in initiating repolarization, and it is distinct from the quasi-instantaneous, inwardly rectifying background current, IK. In atrial cells, IK does not exhibit inactivation, and very long depolarizing clamp steps (20 s) can be applied without producing extracellular K+ accumulation. The possibility of [K+]o accumulation contributing to these slow outward current changes was assessed by (a) comparing reversal potentials measured after short (2 s) and very long (15 s) activating prepulses, and (b) studying the kinetics of IK at various holding potentials and after systematically altering [K+]o. In the absence of [K+]o accumulation, the steady state activation curve (n infinity) and fully activated current-voltage (I-V) relation can be obtained directly. The threshold of the n infinity curve is near -50 mV, and it approaches a maximum at +20 mV; the half-activation point is approximately -16 mV. The fully activated I-V curve of IK is approximately linear in the range -40 to +30 mV. Semilog plots of the current tails show that each tail is a single-exponential function, which suggests that only one Hodgkin-Huxley conductance underlies this slow outward current. Quantitative analysis of the time course of onset of IK and of the corresponding envelope of tails demonstrate that the activation variable, n, must be raised to the second power to fit the sigmoid onset accurately. The voltage dependence of the kinetics of IK was studied by recording and curve-fitting activating and deactivating (tail) currents. The resulting 1/tau n curve is U-shaped and somewhat asymmetric; IK exhibits strong voltage dependence in the diastolic range of potentials. Changes in the [Ca2+]o in the superfusing Ringer's, and/or addition of La3+ to block the transmembrane Ca2+ current, show that the time course and magnitude of IK are not significantly modulated by transmembrane Ca2+ movements, i.e., by ICa. These experimentally measured voltage- and time-dependent descriptors of IK strongly suggest an important functional role for IK in atrial tissue: it initiates repolarization and can be an important determinant of rate-induced changes in action potential duration.
J Gen Physiol 1986 Dec
PMID:A time- and voltage-dependent K+ current in single cardiac cells from bullfrog atrium. 243 58

A theoretical model is presented for voltage clamp of a bundle of cylindrical excitable cells in a double sucrose gap. The preparation in the test node is represented by a single one-dimensional cable (length/diameter ratio approximately) with standard Hodgkin-Huxley kinetics for transmembrane Na current. Imperfections of voltage control due to internal (longitudinal) resistivity and external (radial) resistance in series to the membrane are analysed. The electrical behavior of a fiber is described by the cable equation with appropriate boundary conditions and subsidiary equations reflecting the membrane characteristics. Membrane voltage and current distribution in response to a step command was obtained by numerical integration. The results are described in two papers. The present paper deals with the effect of internal resistivity with the external resistance being neglected. The closed loop response of a fiber displays a strong tendency to oscillate. To stabilize the system a phase lead was inserted and the gain of the control amplifier was reduced. Conditions for stability were examined by Nyquist analysis. When the Na system was activated by a command pulse below ENa, a voltage gradient developed between a depolarization (relative to the command signal) at the end where voltage was monitored and a hyperpolarization at the site of current injection. In spite of a poor voltage control the total measured current appeared to have a smooth transient. With large voltage gradients a small, second inward current was seen. At a low (high) Na conductance maximum peak inward current was larger (smaller) that the current expected from ideal space clamping.
Gen Physiol Biophys 1986 Oct
PMID:Voltage clamp simulations for multifiber bundles in a double sucrose gap: cable complications. 243 82

The effect of temperature (0-22 degrees C) on the kinetics of Na channel conductance was determined in voltage-clamped rabbit and frog skeletal muscle fibers using the triple-Vaseline-gap technique. The Hodgkin-Huxley model was used to extract kinetic parameters; the time course of the conductance change during step depolarization followed m3h kinetics. Arrhenius plots of activation time constants (tau m), determined at both moderate (-10 to -20 mV) and high (+100 mV) depolarizations, were linear in both types of muscle. In rabbit muscle, Arrhenius plots of the inactivation time constant (tau h) were markedly nonlinear at +100 mV, but much less so at -20 mV. The reverse situation was found in frog muscle. The contrast between the highly nonlinear Arrhenius plot of tau h at +100 mV in rabbit muscle, compared with that of frog muscle, was interpreted as revealing an intrinsic nonlinearity in the temperature dependence of mammalian muscle Na inactivation. These results are consistent with the notion that mammalian cell membranes undergo thermotropic membrane phase transitions that alter lipid-channel interactions in the 0-22 degrees C range. Furthermore, the observation that Na channel activation appears to be resistant to this effect suggests that the gating mechanisms that govern activation and inactivation reside in physically distinct regions of the channel.
J Gen Physiol 1987 Feb
PMID:Temperature dependence of Na currents in rabbit and frog muscle membranes. 243 39

There has been some uncertainty in the past as to the origin of the rising phase of the gating current. We present evidence here that proves that the gating current does not have a rising phase and that the observed rising phase is due to an uncompensated series resistance in the Frankenhaeuser-Hodgkin (F-H) space. When a squid giant axon is bathed in a solution that is 10-20% hyperosmotic with respect to the internal solution, the rising phase of the gating current is eliminated. In parallel with this, a component of the capacity transient (time constant, 20 microseconds) is reduced so that the capacity transient now appears to be closer to a single fast (5-10 microseconds) component. These changes in the capacity transient and gating current occur without altering the amount of charge moved in either. This indicates that the charge is simply redistributed in time. The gating current without a rising phase can still be immobilized by inactivation. Supporting evidence is provided by measuring the accumulation and washout of K+ from the F-H space. It was found that K+ washes out 35% faster when the axon is bathed in hyperosmotic solution. It was estimated that the F-H space thickness (theta) increased 2.5 +/- 0.4-fold (mean +/- SEM) in hyperosmotic solution. Similarly, K+ accumulation in the F-H space was decreased, leading to an estimate of a 5 +/- 1.4-fold increase in theta in hyperosmotic solution. These results are consistent with the simple structural model presented.
J Gen Physiol 1987 Apr
PMID:Sodium channel gating currents. Origin of the rising phase. 243 70

The ionic permeability of a voltage-dependent Cl channel of rat hippocampal neurons was studied with the patch-clamp method. The unitary conductance of this channel was approximately 30 pS in symmetrical 150 mM NaCl saline. Reversal potentials interpreted in terms of the Goldman-Hodgkin-Katz voltage equation indicate a Cl:Na permeability ratio of approximately 5:1 for conditions where there is a salt gradient. Many anions are permeant; permeability generally follows a lyotropic sequence. Permeant cations include Li, Na, K, and Cs. The unitary conductance does not saturate for NaCl concentrations up to 1 M. No Na current is observed when the anion Cl is replaced by the impermeant anion SO4. Unitary conductance depends on the cation species present. The channel is reversibly blocked by extracellular Zn or 9-anthracene carboxylic acid. Physiological concentrations of Ca or Mg do not affect the Na:Cl permeability ratio. The permeability properties of the channel are consistent with a permeation mechanism that involves an activated complex of an anionic site, an extrinsic cation, and an extrinsic anion.
J Gen Physiol 1987 Oct
PMID:Anion and cation permeability of a chloride channel in rat hippocampal neurons. 244 1

The calcium current of bullfrog sympathetic neurons activates and deactivates rapidly (tau less than 3 ms). For brief depolarizations, the current can be fit reasonably well by a Hodgkin-Huxley-type model with a single gating particle of charge +3. With 2 mM Ca2+ as the charge carrier, half-maximal activation occurs at approximately -5 mV, near the voltage where activation and deactivation are slowest. When extracellular divalent ion concentrations are reduced, monovalent ions (e.g., Na+ and methylammonium) produce kinetically similar inward currents. Current carried by Ba2+ is blocked by Cd2+ at micromolar concentrations, and by 100 nM omega-conotoxin. Commercially available saxitoxin blocks the current, but different batches have quantitatively different potency. The dihydropyridine agonist Bay K 8644 induces a slight shift in activation kinetics to more negative voltages, with little effect on the peak current. Nifedipine at least partially reverses the effect of Bay K 8644, but has little effect on its own. Muscarinic agonists and other ligands that inhibit the M-type potassium current of frog sympathetic neurons have weak inhibitory effects on the calcium current as well. One interpretation of these results is that the N-type calcium current predominates in these cells, with a minor contribution of L-type current.
J Gen Physiol 1989 Jul
PMID:Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology. 247 59

Starting from the observation that using a conventional potential clamp device for membrane current measurements in Ranvier nodes neither the kinetics of sodium currents nor the constant field concept agree satisfactorily with the Hodgkin-Huxley-Frankenhaeuser (HHF)-formalism, an extendend measuring system has been developed. The extensions introduced base largely on physical implications of myelinated nerve fibres which give rise 1. to systematic distortions of any current records at the high frequency end and 2. to current proportional deviations of the membrane potential from desired potential values. In addition, we provided to meet any unwanted current load during membrane current measurements and to push the time resolution of the measuring system to the highest possible value. After having tested thoroughly the new circuitry by appropriate physical methods, from sodium current measurements the following conclusions were drawn: 1. Occasional deviations of sodium current kinetics near the sodium equilibrium potential from the predictions of the HHF-formalism are measurement errors. 2. The constant field formalism holds for sodium currents in the potential range of biological relevance only. 3. Instantaneous sodium current measurements, however, are of unsatisfactory significance because for this kind of experiments the time resolution of the measuring system used might be still too low.
Gen Physiol Biophys 1989 Oct
PMID:High standard one-loop potential clamp device for Ranvier nodes. 259 24


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>