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)

1. The effect of extracellular K+ on membrane currents of bull frog (Rana catesbeiana) taste receptor cells (TRCs) was investigated by the patch clamp and fast perfusion techniques. Extracellular K+ (2.5-90 mM) increased a TRC resting conductance and enhanced both inward and outward whole-cell currents. 2. To isolate the inward current activated by external potassium (PA current), TRCs were dialysed with 110 mM NMGCl while extracellular NaCl was replaced with NMGCl. Under these conditions, the PA current displayed an S-shaped current-voltage (I-V) curve in the -100 to 100 mV range. Extracellular Rb+ and NH4+, but not Li+, Na+ or Cs+, evoked similar currents. 3. The PA current reversal potential (Vr) did not follow the equilibrium K+ potential under experimental conditions. Therefore, K+ ions were not the only current carriers. The influence of other ions on the PA current Vr indicated that the channels involved are permeable to K+ and H+ and much less so to Na+, Ca2+ and Mg2+. Relative permeabilities were estimated on the basis of the Goldman-Hodgkin-Katz equation as follows: PH:PK:PNa = 4000:1:0.04. 4. All I-V curves of the PA current were nearly linear at low negative potentials. The slope conductance at these voltages was used to characterize the dependence of the PA current on external K+ and H+. The slope conductance versus K+ concentration was fitted by the Hill equation. The data yielded a half-maximal concentration, K1/2 = 19 +/- 3 mM and a Hill coefficient, nH = 1.53 +/- 0.36 (means +/- S.E.M.). 5. The dependence of the mean PA current and the current variance on the K+ concentration indicated a rise in the open probability of the corresponding channels as extracellular K+ was increased. With 110 mM KCl in the bath, the single channel conductance was estimated at about 6 pS. Taken together, the data suggest that extracellular K+ may serve as a ligand to activate specific small-conductance cation channels (PA channels). The mean number of the PA channels per TRC was estimated as at least 2000. 6. Extracellular Ba2+, Cd2+, Co2+, Ni2+ and Cs+ blocked the PA current in a potential-dependent manner. The PA current was blocked by Cs+ as quickly as the blocker could be applied (approximately 15 ms). The time course of the divalent cation block was well fitted by a single exponential function. The time constants were estimated at 26.5 +/- 1.9, 41.7 +/- 3.1, 56.1 +/- 4.2 and 370 +/- 18 ms at 1 mM Cd2+, Co2+, Ni2+ and Ba2+, respectively. The blocker efficiency at negative voltages followed the sequence: Cs+ > Cd2+ > Ba2+ > Ni2+ > Co2+. 7. The data indicate that protons and divalent blockers act within the PA channel pore and that H+ and the divalent ions probably act via similar mechanisms to affect the PA current. These observations and the strong pH dependence of the PA current Vr suggest that H+ occupation of the PA channel pore leading to interruption of K+ flux is the main mechanism of the pH dependence of the PA current. 8. Extracellular K+ enhanced the sensitivity of isolated TRCs to bath solution acidification due to activation of the PA channels. With 10 mM K+ in the bath, half-maximal depolarization of the TRCs was observed at pH values of 6.4-6.8. The possible role of the PA channels in sour transduction is discussed.
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PMID:Extracellular K+ activates a K(+)- and H(+)-permeable conductance in frog taste receptor cells. 951 2

Inward Ca2+ current through voltage-gated Ca2+ channels was recorded from freshly dissociated crayfish X-organ (XO) neurones using the whole-cell voltage-clamp technique. Changing the holding potential from -50 to -90 mV had little effect on the characteristics of the current-voltage relationship: neither the time course nor the amplitude of the Ca2+ current was affected. Inactivation of the Ca2+ current was observed over a small voltage range, between -35 and -10 mV, with half-inactivation at -20 mV. The activation of the Ca2+ current was modelled using Hodgkin-Huxley kinetics. The time constant of activation, &tgr; m, was 568+/-66 micros at -20 mV and decreased gradually to 171+/-23 micros at 40 mV (means +/- s.e.m., N=5). The steady-state activation, m(infinity), was fitted with a Boltzmann function, with a half-activation voltage of -7.45 mV and an apparent threshold at -40 mV. The instantaneous current-voltage relationship was adjusted using the Goldman-Hodgkin-Katz constant-field equation, giving a permeation of 4.95x10(-5 )cm s-1. The inactivation of the Ca2+ current in XO neurones was dependent on previous entry of Ca2+. Using a double-pulse protocol, the inactivation was fitted to a U-shaped curve with a maximal inactivation of 35 % at 30 mV. The time course of the recovery from inactivation was fitted with an exponential function. The time constants were 17+/-2.6 ms for a prepulse of 10 ms and 31+/-3.2 ms for a prepulse of 20 ms. The permeability sequence of the Ca2+ channels was as follows: Ba2+>Sr2+~Ca2+>>Mg2+. Other divalent cations blocked the Ca2+ current, and their effects were voltage-dependent; the potency of blockage was Cd2+~Zn2+>>Co2+~Ni2+. The peptide &ohgr; -agatoxin-IVA, a selective toxin for P-type Ca2+ channels, blocked 85 % of the Ca2+ current in XO neurones at 200 nmol l-1, but the current was insensitive to dihydropyridines, phenylalkylamines, &ohgr; -conotoxin-GVIA and &ohgr; -conotoxin-MVIIC, which are blockers of L-, N- and Q-type Ca2+ channels, respectively. From the voltage- and Ca2+-dependent kinetics, the higher permeability to Ba2+ than to Ca2+ and the higher sensitivity of the current to Cd2+ than to Ni2+, we conclude that the Ca2+ current in XO neurones is generated by high-voltage-activated (HVA) channels. Furthermore, its blockage by &ohgr; -agatoxin-IVA suggests that it is mainly generated through P-type Ca2+ channels.
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PMID:P-type Ca2+ current in crayfish peptidergic neurones. 991 50

Magnesium and zinc are the elements having essential roles in regulation of cell growth, division and differentiation. There have been some studies in the literature suggesting an association between the deficiency of these elements and the development of malignant disorders. In this study hair and serum zinc and magnesium levels were investigated in children with acute lymphoblastic leukemia (ALL) and malignant lymphoma (ML) at the time of initial diagnosis. Ten children with T-cell ALL, 10 children with B-precursor ALL, 5 children with Burkitt's Lymphoma (BL), 11 children with Hodgkin's lymphoma (HL), 10 children with non-Burkitt non-Hodgkin's lymphoma (NBNHL) and 12 age and sex matched healthy children as a control group were included in the study. Mean hair magnesium levels in all of the groups of the patients were lower than the levels in the control group but the difference was statistically significant only in the children with T cell ALL comparable to the controls (28.9+/-3.9 microg/g and 87.6+/-18.5 microg/g respectiveley, p<0,05). Mean serum magnesium levels in all the cohorts were not significantly different than those in controls (p>0.05 in each comparison). Mean hair zinc levels in the patients with T-cell, B-precursor ALL, BL, HL, NBNHL were 103.4+/-14.6 microg/g, 100.9+/-7.8 microg/g, 91.1+/-19 microg/g, 72.5+/-9.1 microg/g, 103.2+/-12.2 microg/g respectively. Each of these levels were significantly lower than the mean hair zinc levels of the control group (141.2+/-9.6 microg/g, p<0.05 in each comparison). Although mean serum zinc levels in all of the groups were also decreased, the differences were statistically significant only in the groups with B-precursor ALL, HL and NBNHL (75.9+/-5.29 microg/dl, 68.6+/-7.3 microg/dl, 85.7+/-5.5 microg/dl respectively) when compared with controls (105.1+/-9.9 microg/dl, p<0.05 in each comparison). Hair magnesium and zinc levels showed a positive correlation with each other in all the groups (r congruent with 0.5). No significant difference was found in the mean hair/serum magnesium and zinc levels between malnourished and nonmalnourished patients. In conclusion, regarding the results of our study and previous data in the literature chronic magnesium and zinc deficiency seems to be associated with the development of ALL and malignant lymphoma in a group of patients.
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PMID:High prevelance of chronic magnesium deficiency in T cell lymphoblastic leukemia and chronic zinc deficiency in children with acute lymphoblastic leukemia and malignant lymphoma. 1134 38

We combined the Hodgkin-Huxley equations and a 36-state model of gap junction channel gating to simulate electrical signal transfer through electrical synapses. Differently from most previous studies, our model can account for dynamic modulation of junctional conductance during the spread of electrical signal between coupled neurons. The model of electrical synapse is based on electrical properties of the gap junction channel encompassing two fast and two slow gates triggered by the transjunctional voltage. We quantified the influence of a difference in input resistances of electrically coupled neurons and instantaneous conductance-voltage rectification of gap junctions on an asymmetry of cell-to-cell signaling. We demonstrated that such asymmetry strongly depends on junctional conductance and can lead to the unidirectional transfer of action potentials. The simulation results also revealed that voltage spikes, which develop between neighboring cells during the spread of action potentials, can induce a rapid decay of junctional conductance, thus demonstrating spiking activity-dependent short-term plasticity of electrical synapses. This conclusion was supported by experimental data obtained in HeLa cells transfected with connexin45, which is among connexin isoforms expressed in neurons. Moreover, the model allowed us to replicate the kinetics of junctional conductance under different levels of intracellular concentration of free magnesium ([Mg2+]i), which was experimentally recorded in cells expressing connexin36, a major neuronal connexin. We demonstrated that such [Mg2+]i-dependent long-term plasticity of the electrical synapse can be adequately reproduced through the changes of slow gate parameters of the 36-state model. This suggests that some types of chemical modulation of gap junctions can be executed through the underlying mechanisms of voltage gating. Overall, the developed model accounts for direction-dependent asymmetry, as well as for short- and long-term plasticity of electrical synapses. Our modeling results demonstrate that such complex behavior of the electrical synapse is important in shaping the response of coupled neurons.
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PMID:Functional asymmetry and plasticity of electrical synapses interconnecting neurons through a 36-state model of gap junction channel gating. 2838 20


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