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

1. The generation of action potentials elicited from enzymatically dispersed ventricular cells from the frog, Rana catesbeiana, has been shown to be due to the influx of both Na+ and Ca2+. The maximum rate of rise, the amplitude and the duration at 50% repolarization of the action potential were estimated to be 26.4 +/- 5.1 V/s (n = 8), 110 +/- 2.7 mV (n = 8) and 601 +/- 180 ms (n = 8) at 15 degrees C, respectively. 2. Inward Na+ current (INa) was studied in these ventricular cells by the whole-cell patch clamp technique in a medium where Ca2+ current was eliminated by substituting extracellular Mg2+ for Ca2+ and K+ current was suppressed by applying Cs+ intracellularly. All the voltage clamp experiments were carried out at 4 degrees C. 3. INa elicited by single depolarizing steps from a holding potential (VH) of -80 mV had a threshold of -50 mV and was maximal at -20 mV. Peak currents in normal Ringer solution containing 113.5 mM-Na+ were of the order of 0.01-0.02 mA/cm2. Maximum Na+ conductance (gNa) was calculated to be 5.9 mS/cm2. 4. Under normal conditions the reversal potential for INa was determined to be 50 mV, which is close to the value predicted from the Nernst equation. The reversal potential changed by 59 mV per tenfold change in the activity of extracellular Na+ (aNa). 5. The instantaneous relation between INa tail currents and membrane potential is linear, crossing the abscissa at the reversal potential for INa. 6. Reconstructions of INa were made in terms of the parameters of the Hodgkin-Huxley model for the squid axon, using constants obtained from the frog ventricular cells. 7. The falling phase of INa and the development of inactivation measured by the double-pulse method could be well fitted by a single-exponential function. 8. The time course for recovery of INa from inactivation exhibited a single time constant.
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PMID:A study of the electrical characteristics of sodium currents in single ventricular cells of the frog. 245 74

1. Using the method of Hodgkin, McNaughton & Nunn (1985) for rapidly changing the extracellular medium, we analysed the effect of divalent cations on the photocurrent of isolated retinal rods of the tiger salamander. 2. When the extracellular NaCl was replaced by equiosmolar amounts of BaCl2, SrCl2, CaCl2, MgCl2 and MnCl2 the efficacy in carrying the photocurrent at early times was Ba2+ greater than Sr2+ greater than Ca2+ greater than Mg2+ greater than Mn2+. At early times Ba2+ could carry a photocurrent similar to or larger than that carried by Na+. 3. The photocurrent carried by Ba2+ increased by about 50% when [Ca2+]o was reduced from 1 to 0.1 mM. In the presence of 0.1 mM-Ca2+ in the extracellular medium the photocurrent carried by Ba2+ saturated when [Ba2+]o was close to 50 mM and was half-activated at 15 mM [Ba2+]o. 4. The photocurrent which can be carried by Sr2+ is not larger than that carried by Ba2+ and does not saturate for [Sr2+]o up to 70 mM. 5. When extracellular Na+ is replaced by the impermeant organic ion choline it is possible to observe a transient photocurrent which is carried by Ca2+. This current has a maximal value of about 11 pA and has a half-activation constant of about 50 microM. 6. Movements of Mg2+ across the light-sensitive channel can be seen only when extracellular Ca2+ is reduced below 10 microM. Under these conditions the maximal photocurrent which can be carried by Mg2+ at early times is about 8 pA and has a half-activation of about 2 mM. Under normal conditions Mn2+ is hardly permeable through the light-sensitive channel. 7. It is concluded that the selectivity of the light-sensitive channel in the low ionic concentration range is Ca2+ greater than Sr2+ greater than Ba2+ greater than Mg2+ greater than Na+.
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PMID:The ionic selectivity of the light-sensitive current in isolated rods of the tiger salamander. 246 83

1. By using the method of Hodgkin, McNaughton & Nunn (1985) for rapidly changing the extracellular medium, we analysed the effect of the organic compound IBMX (3-isobutyl-1-methylxanthine) on the movement of divalent cations through the light-sensitive channels of isolated retinal rods of the tiger salamander. 2. When the rod is treated with 0.5 mM-IBMX it is possible to observe photocurrents larger than 50 pA carried by Ba2+, Sr2+, Ca2+, Mg2+ and Mn2+. Under these conditions Ca2+, Mg2+ and Mn2+ carry photocurrents of similar amplitude, while Ba2+ and Sr2+ usually carry larger photocurrents. 3. The movement of Mn2+ through the light-sensitive channel, which is hardly detected under normal conditions, can also be observed after treating the rod for a few seconds with a solution containing 35 mM[Na+]o and 10(-7) M[Ca2+]o. Under these conditions the photocurrent carried by Mn2+ is fully saturated in the presence of 1 mM-extracellular Mn2+. 4. When the rod is pre-treated with an extracellular solution containing 0.5 mM-IBMX the maximal photocurrent which can be carried by 10 mM [Ca2+]o increases from about 10 pA to approximately 200 pA. In these conditions the half-activation of the Ca2+ current is between 1 and 10 mM, that is 20-50 times higher than in normal conditions (Menini, Rispoli & Torre, 1988). 5. When the rod is pre-treated with an extracellular solution containing 0.5 mM-IBMX the half-activation of the photocurrent which can be carried by Mg2+, Ba2+ and Sr2+ is equivalent to or greater than 10 mM. In the absence of pre-treatment with IBMX the half-activation of the photocurrent carried by Mg2+, Ba2+ and Sr2+ is less than 5 mM. 6. We conclude that the light-sensitive channel can exist in at least two distinct open states. The selectivity of the channel in the first open state is as described in a previous paper (Menini et al. 1988). Mn2+, which is hardly permeable through the light-sensitive channel in the first open state, can move through the light-sensitive channel in the second open state. Ca2+, Mg2+, Ba2+ and Sr2+ permeate more freely through the light-sensitive channel in the second open state, probably because the electrostatic interactions between these ions and the channel are less strong.
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PMID:The modulation of the ionic selectivity of the light-sensitive current in isolated rods of the tiger salamander. 247 69

The non-selective channel for monovalent cations of cultured brown adipocytes was studied concerning its permeability to alkali metal ions, NH4+, Tris+, Ca2+, and Ba2+. Experiments were done by means of the patch clamp technique using inside-out patches. With symmetrically increasing sodium concentrations the ion fluxes saturated. They are described by a dissociation constant (KNa) of 155 mmol/l and a maximum single channel conductance of 50 pS. Permeabilities were determined in relation to those for sodium yielding values of 0.80 for potassium and 1.55 for ammonium. The complete permeability sequence for ammonium and the alkali metals is: NH4+ greater than Na+ greater than Li+ greater than K+ greater than or equal to Rb+ congruent to Cs+ . Ca2+ and Ba2+ as well as the buffer ion Tris+ are not able to pass the channel measurably. It is shown that the conductance behaviour of the non-selective channel is not sufficiently described by the Goldman-Hodgkin-Katz theory. Deviations from independence are saturation with increased activity of the permeant ion and non-linear current voltage relations in symmetrical solutions. A simple two barrier model with one binding site in the center of the electric field is shown to be more appropriate.
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PMID:Permeability of the non-selective channel in brown adipocytes to small cations. 247 15

The effect of cadmium on the light-sensitive current of isolated rods of the tiger salamander was analysed by rapidly changing the ionic medium using the technique of Hodgkin et al. (1985). Addition of millimolar amounts of cadmium to the extracellular medium caused a rapid, but transient, decrease of the photocurrent. The effect of cadmium on the movement of divalent cations, such as Ba2+ and Ca2+, differs according to the experimental protocol: when cadmium is introduced into the bathing medium at the same time as Ca2+ or Ba2+, it blocks the entry of these ions into the rod; and when the rod is exposed to cadmium first for a few seconds the entry of Ca2+ and Ba2+ is enhanced. The effect of cadmium is best explained as a dual effect: firstly, an external effect on the channel, and secondly, by metabolic changes, which are caused by a drop of intracellular Ca2+.
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PMID:The effect of cadmium on the light-sensitive current of isolated rods of the tiger salamander. 247 89

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.
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PMID:Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology. 247 59

The kinetic and steady-state characteristics of calcium currents in cultured bovine adrenal chromaffin cells were analyzed by the patch-clamp technique. Whole cell inward Ca2+ currents, recorded in the presence of either 5.2 or 2.6 mM Ca2+ exhibited a single, noninactivating component. To analyze the effects of Ca2+ and Bay K-8644 on the kinetics of the Ca2+ currents, we used a modified version of the Hodgkin-Huxley empirical model. At physiological [Ca2+] (2.5 mM) the midpoint of the steady-state Ca2(+)-channel activation curve lay at -6.9 mV. Increasing the [Ca2+] to 5.2 mM shifted the midpoint by -4.3 mV along the voltage axis. At the midpoint, changes in potential of 7.8 mV (for 5.2 mM Ca2+) and 9.2 mV (for 2.5 mM Ca2+) induced an e-fold change in the activation of the current. Increasing [Ca2+]o from 2.5 to 5.2 mM induced a marked increase in the rate constant for turning on the Ca2+ permeability. Conductances were estimated from the slope of the linear part of the current-voltage relationships as 8.7 and 4.2 nS in the presence of 5.2 and 2.5 mM Ca2+, respectively. Incubation of the cells in the presence of Bay K-8644 at increasing concentrations from 0.001 to 0.1 microM increased the slope conductance from 4.2 to 9.6 nS. Further increases in the concentration of Bay K-8644 from 1 to 100 microM induced a marked reduction in the conductance to 1.1 nS. In the presence of Bay K-8644 (0.1 microM) the midpoint of the activation curve was shifted by 6.1 mV towards more negative potentials, i.e., from -6.9 to -13 mV. At the midpoint potential of -13 mV, a change in potential of 6.9 mV caused an e-fold change in Ca2+ permeability. The kinetic analysis showed that Bay K-8644 significantly reduced the size of the rate constant for turning off the Ca2+ permeability.
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PMID:Effects of calcium and Bay K-8644 on calcium currents in adrenal medullary chromaffin cells. 248 62

1. The calcium currents evoked by membrane depolarization in the mature and intact rat sympathetic neurone have been studied at 37 degrees C using two-electrode voltage-clamp analysis. 2. Under conditions that eliminate Na+ and K+ currents and 5 mM-external Ca2+, inward currents were observed that activated at about -30 mV and reached maximum amplitude between 0 and +10 mV with time-to-peak values (2.7-1.9 ms) decreasing with increasing membrane depolarization. Thereafter, calcium current (ICa) decayed to a virtually zero level with maintained depolarization. Two exponentials were required to describe the total inactivation process. The faster rate (tau = 29.3-17.6 ms) is ten times the slower rate and proved to be only slightly voltage-dependent. Double-pulse experiments gave a similar time course of turn-off. 3. No steady-state inactivation was removed at holding potentials between -40 and -70 mV and indirect data suggest that all the ICa was available at -50 mV. Within the -30 to -50 mV holding potential range no significant modifications either in the final amount of ICa inactivation or in the inactivation time constant values were detected. 4. After an initial 100 ms, recovery from inactivation followed a single-exponential process with a mean time constant value of 1.54 s at -50 mV. 5. The kinetics of ICa observed in this neurone were consistent with the existence of a single class of Ca2+ channels. For times up to 20 ms, ICa is described reasonably well by a Hodgkin-Huxley c2hc scheme. The activation time constant was 0.57 ms close to threshold and 0.29 ms at +30 mV. Deactivation occurred with a similar fast time course. The steady-state value of the variable c was evaluated in the -40 to +20 mV voltage range: 9.9 mV are required to change c infinity e-fold. 6. Following previous analyses, we have formulated a mathematical model which incorporates the present ICa kinetic equations with Hodgkin-Huxley-type gating mechanisms for INa, IA and IK(V) conductances. The Ca2+ load of the neurone proved to be basically an 'off' effect and to be governed by the duration of the action potential falling phase. The model is consistent with the experimental observations indicating that Ca2+ channels probably do not have an important direct electrical function in the sympathetic neurone spike at normal membrane potential levels.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Calcium currents in the normal adult rat sympathetic neurone. 255 30

The sensitivity of the Ca2+ pumping ATPase of bovine cardiac sarcolemma (SL) to changes in membrane potential was studied in a preparation of sealed SL vesicles. Membrane potential was imposed by preincubating the vesicles in media of defined ion composition (K+, Cl-, choline+ and gluconate-) and diluting into media of differing ion composition. The durations of the ion gradients and relative ion permeabilities were determined in separate experiments by the dependence of the half time for net K+ (or choline+) movement coupled with these anions (Cl- or gluconate-), registered by the fluorescence of 1-anilino-8-naphthalene sulfonate (Chiu, V.C.K., Haynes, D.H. 1980. J. Membrane Biol. 56:203-218). Relative permeabilities were: 1.0, K+; greater than or equal to 10.0, 1 microM valinomycin-K+; 4.0, Cl-; 0.66, choline+; 0.38, gluconate-. Durations of the gradients ranged between 17 sec (KCl, valinomycin) to 195 sec (K(+)-gluconate-). In separate experiments, active Ca2+ uptake was monitored using chlorotetracycline (CTC) fluorescence, a technique validated by 45-Ca2+ measurements (Dixon, D., Brandt, N., Haynes, D.H. 1984. J. Biol. Chem. 259:13737-13741). Active Ca2+ uptake was initiated in the presence of monovalent ion gradients. The values of the membrane potentials (Em) imposed by the monovalent ion gradients were calculated using the ion concentrations, their relative permeabilities and the Goldman-Hodgkin-Katz equation. No effect of membrane potential on transport rate was observed (less than or equal to 4%, for 5-7% SD) for imposed potentials as extreme as greater than or equal to +71 and less than or equal to -67 mV. Formal analysis shows that the above observations are not compatible with models in which the Ca2+ pumping ATPase functions in an electrogenic or charge-uncompensated fashion. Further experimentation showed that the pump rate is slowed when uptake is measured at less-than-adequate concentrations of buffer (5 vs. 25 mM HEPES/Tris). This, together with further control experiments using nigericin and FCCP, gave evidence that the pump requires a source of counter-transportable H+ in the vesicle lumen. The above experimentation also underlines the need for control of internal pH to obviate erroneous interpretation of ion perturbation experiments. The results are compared with results obtained with the Ca2+ ATPase pump of skeletal sarcoplasmic reticulum.
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PMID:Ca2+ pumping ATPase of cardiac sarcolemma is insensitive to membrane potential produced by K+ and Cl- gradients but requires a source of counter-transportable H+. 256 63

The active and passive electrical properties of the after-hyperpolarizing (AH) cell of the guinea-pig myenteric plexus were analysed using a single-electrode voltage or current clamp. Action potentials were compared under normal conditions, in the presence of tetrodotoxin (TTX) and in the presence of both TTX and tetraethylammonium chloride (TEA). Calcium action potentials were studied by examining their calcium dependence, the actions of manganese and the effect of substituting barium for calcium. The maximum rate of rise of the action potential did not increase in calcium concentrations above 10 mM. The half-saturation concentration was 2 mM-calcium. AH cells exhibited five predominant currents consisting of an inward sodium current, an inward calcium current and three outward currents. There was a transient outward current which was inactivated at holding potentials more positive than -65 mV and was suppressed by 4-aminopyridine and barium but not by external TEA. A second outward current observed in the presence of 10 mM-external TEA had properties consistent with that of the delayed rectifier (Hodgkin & Huxley, 1952). A third outward current was the calcium-dependent slow after-hyperpolarizing current (Hirst, Johnson & van Helden, 1985). The voltage dependence, the action of calcium antagonists, the effect of barium substitution and the temporal characteristics of calcium currents were studied. The peak calcium current density was in excess of 100 microA/cm2 in 2.5 mM-calcium solution at 35 degrees C for depolarizations to -10 mV. Calcium currents showed at least two phases of inactivation. Both calcium and barium currents showed early inactivation with decay occurring over the first 10-40 ms. The calcium-activated current precluded direct measurement of slow inactivation of the calcium current. Barium currents studied over the first 100-150 ms had a very slow inactivating component.
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PMID:The calcium current in a myenteric neurone of the guinea-pig ileum. 258 Sep 78


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