scholarly journals Permeation of Na+ through a delayed rectifier K+ channel in chick dorsal root ganglion neurons.

1994 ◽  
Vol 104 (4) ◽  
pp. 747-771 ◽  
Author(s):  
M J Callahan ◽  
S J Korn
Keyword(s):  
Dorsal Root Ganglion ◽  
Binding Site ◽  
Dorsal Root ◽  
Reversal Potential ◽  
Dorsal Root Ganglion Neurons ◽  
K Channel ◽  
Delayed Rectifier ◽  
Cation Binding Site ◽  
Voltage Dependent ◽  
Ganglion Neurons

In whole-cell patch clamp recordings from chick dorsal root ganglion neurons, removal of intracellular K+ resulted in the appearance of a large, voltage-dependent inward tail current (Icat). Icat was not Ca2+ dependent and was not blocked by Cd2+, but was blocked by Ba2+. The reversal potential for Icat shifted with the Nernst potential for [Na+]. The channel responsible for Icat had a cation permeability sequence of Na+ > Li+ > TMA+ > NMG+ (PX/PNa = 1:0.33:0.1:0) and was impermeable to Cl-. Addition of high intracellular concentrations of K+, Cs+, or Rb+ prevented the occurrence of Icat. Inhibition of Icat by intracellular K+ was voltage dependent, with an IC50 that ranged from 3.0-8.9 mM at membrane potentials between -50 and -110 mV. This voltage-dependent shift in IC50 (e-fold per 52 mV) is consistent with a single cation binding site approximately 50% of the distance into the membrane field. Icat displayed anomolous mole fraction behavior with respect to Na+ and K+; Icat was inhibited by 5 mM extracellular K+ in the presence of 160 mM Na+ and potentiated by equimolar substitution of 80 mM K+ for Na+. The percent inhibition produced by both extracellular and intracellular K+ at 5 mM was identical. Reversal potential measurements revealed that K+ was 65-105 times more permeant than Na+ through the Icat channel. Icat exhibited the same voltage and time dependence of inactivation, the same voltage dependence of activation, and the same macroscopic conductance as the delayed rectifier K+ current in these neurons. We conclude that Icat is a Na+ current that passes through a delayed rectifier K+ channel when intracellular K+ is reduced to below 30 mM. At intracellular K+ concentrations between 1 and 30 mM, PK/PNa remained constant while the conductance at -50 mV varied from 80 to 0% of maximum. These data suggest that the high selectivity of these channels for K+ over Na+ is due to the inability of Na+ to compete with K+ for an intracellular binding site, rather than a barrier that excludes Na+ from entry into the channel or a barrier such as a selectivity filter that prevents Na+ ions from passing through the channel.

Axotomy- and Autotomy-Induced Changes in Ca2+and K+ Channel Currents of Rat Dorsal Root Ganglion Neurons

2001 ◽  
Vol 85 (2) ◽  
pp. 644-658 ◽  
Author(s):  
Fuad A. Abdulla ◽  
Peter A. Smith
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Low Voltage ◽  
Cell Types ◽  
Dorsal Root Ganglion Neurons ◽  
Small Cells ◽  
K Channel ◽  
Delayed Rectifier ◽  
Channel Current ◽  
Ganglion Neurons

Sciatic nerve section (axotomy) increases the excitability of rat dorsal root ganglion (DRG) neurons. The changes in Ca2+ currents, K+ currents, Ca2+-sensitive K+ current, and hyperpolarization-activated cation current ( I H) that may be associated with this effect were examined by whole cell recording. Axotomy affected the same conductances in all types of DRG neuron. In general, the largest changes were seen in “small” cells and the smallest changes were seen in “large” cells. High-voltage–activated Ca2+-channel current (HVA- I Ba) was reduced by axotomy. Although currents recorded in axotomized neurons exhibited increased inactivation, this did not account for all of the reduction in HVA- I Ba. Activation kinetics were unchanged, and experiments with nifedipine and/or ω-conotoxin GVIA showed that there was no change in the percentage contribution of L-type, N-type, or “other” HVA- I Bato the total current after axotomy. T-type (low-voltage–activated) I Ba was not affected by axotomy. Ca2+-sensitive K+conductance ( g K,Ca) appeared to be reduced, but when voltage protocols were adjusted to elicit similar amounts of Ca2+ influx into control and axotomized cells, I K,Ca(s) were unchanged. After axotomy, Cd2+-insensitive, steady-state K+ channel current, which primarily comprised delayed rectifier K+ current ( I K), was reduced by about 60% in small, medium, and large cells. These data suggest that axotomy-induced increases in excitability are associated with decreases in I K and/or decreases in g K,Ca that are secondary to decreased Ca2+-influx. Because I H was reduced by axotomy, changes in this current do not contribute to increased excitability. The amplitude and inactivation of I Ba in all cell types was changed more profoundly in animals that exhibited self-mutilatory behavior (autotomy). The onset of this behavior corresponded with significant reduction in I Ba of large neurons. This finding supports the hypothesis that autotomy, that may be related to human neuropathic pain, is associated with changes in the properties of large myelinated sensory neurons.

scholarly journals Chronic compression of mouse dorsal root ganglion alters voltage-gated sodium and potassium currents in medium-sized dorsal root ganglion neurons

2011 ◽  
Vol 106 (6) ◽  
pp. 3067-3072 ◽  
Author(s):  
Ni Fan ◽  
David F. Donnelly ◽  
Robert H. LaMotte
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Small Diameter ◽  
Radicular Pain ◽  
Dorsal Root Ganglion Neurons ◽  
Delayed Rectifier ◽  
Drg Neurons ◽  
Voltage Dependent ◽  
Ganglion Neurons

Chronic compression (CCD) of the dorsal root ganglion (DRG) is a model of human radicular pain produced by intraforaminal stenosis and other disorders affecting the DRG, spinal nerve, or root. Previously, we examined electrophysiological changes in small-diameter lumbar level 3 (L3) and L4 DRG neurons treated with CCD; the present study extends these observations to medium-sized DRG neurons, which mediate additional sensory modalities, both nociceptive and non-nociceptive. Whole-cell patch-clamp recordings were obtained from medium-sized somata in the intact DRG in vitro. Compared with neurons from unoperated control animals, CCD neurons exhibited a decrease in the current threshold for action potential generation. In the CCD group, current densities of TTX-resistant and TTX-sensitive Na+ current were increased, whereas the density of delayed rectifier voltage-dependent K+ current was decreased. No change was observed in the transient or “A” current after CCD. We conclude that CCD in the mouse produces hyperexcitability in medium-sized DRG neurons, and the hyperexcitability is associated with an increased density of Na+ current and a decreased density of delayed rectifier voltage-dependent K+ current.

Variation in IH, IIR, and ILEAK between acutely isolated adult rat dorsal root ganglion neurons of different size

1994 ◽  
Vol 71 (1) ◽  
pp. 271-279 ◽  
Author(s):  
R. S. Scroggs ◽  
S. M. Todorovic ◽  
E. G. Anderson ◽  
A. P. Fox
Keyword(s):  
Dorsal Root Ganglion ◽  
Action Potentials ◽  
Dorsal Root ◽  
Membrane Surface ◽  
Small Diameter ◽  
Reversal Potential ◽  
Dorsal Root Ganglion Neurons ◽  
Time Dependent ◽  
Drg Neurons ◽  
Ganglion Neurons

1. The distribution of IH, IIR, and ILEAK was studied in different diameter rat dorsal root ganglion (DRG) neuron cell bodies (neurons). DRG neurons were studied in three diameter ranges: small (19–27 microns), medium (33–37 microns), and large (44-54 microns). IH was defined as a slowly activating inward current evoked by hyperpolarizing voltage steps from a holding potential (HP) of -60 mV, and blocked by 1 mM Cs2+ but not 1 mM Ba2+. Inward rectifier current (IIR) was defined as a rapidly activating current evoked by hyperpolarizations from HP -60 mV, which rectified inwardly around the reversal potential for potassium (EK), and was completely blocked by 100 microM Ba2+. ILEAK was defined as an outward resting current at HP -60 mV, which did not rectify and was blocked by 100 microM Ba2+ but not by 2 mM Cs+. 2. IH was observed in 23 of 23 large, 11 of 12 medium, and in 9 of 20 small diameter DRG neurons tested. Peak IH normalized to membrane surface area was significantly greater in large than in medium or small diameter DRG neurons expressing IH. All neurons exhibiting IH under voltage clamp conditions had short duration action potentials and exhibited time-dependent rectification under current clamp conditions, properties similar to A-type DRG neurons. The 11 small diameter neurons not expressing IH had long duration action potentials and did not exhibit time-dependent rectification, properties similar to C-type DRG neurons. 3. IIR was detected in 18 of 22 medium diameter neurons tested.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Slow sodium conductances of dorsal root ganglion neurons: intraneuronal homogeneity and interneuronal heterogeneity

1994 ◽  
Vol 72 (6) ◽  
pp. 2796-2815 ◽  
Author(s):  
M. A. Rizzo ◽  
J. D. Kocsis ◽  
S. G. Waxman
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Half Time ◽  
Drg Neurons ◽  
Patch Clamp Technique ◽  
Adult Rat ◽  
Voltage Dependent ◽  
Order Of Magnitude ◽  
Ganglion Neurons

1. Voltage-dependent Na+ conductances were studied in small (18-25 microns diam) adult rat dorsal root ganglion (DRG) neurons with the use of the whole cell patch-clamp technique. Na+ currents were also recorded from larger (44-50 microns diam) neurons and compared with those of the small neurons. 2. The predominant Na+ conductance in the small neurons was selective over tetramethylammonium by at least 10-fold and was resistant to 1 microM external tetrodotoxin (TTX). Na+ conductances in many larger DRG neurons were kinetically faster and, in contrast, were blocked by 1 microM TTX. 3. The Na+ conductance in the small neurons was kinetically slow. Activation half-times were voltage dependent and ranged from 2 ms at -20 mV to 0.7 ms at +50 mV. Approximately 50% of the activation half-time was comprised of an initial delay. Inactivation half-times were voltage dependent and ranged from 11 ms at -20 mV to 2 ms at +50 mV. 4. Peak slow Na+ conductances were near maximal with conditioning potentials negative to -120 mV and were significantly reduced or eliminated with conditioning potentials positive to -40 mV. The slow Na+ conductance increased gradually with test potentials extending from -40 to +40 mV. In some cells the conductance could be saturated at +10 mV. Peak conductance/voltage relationships, although stable in a given neuron, revealed marked variability among neurons, spanning > 20- and 50-mV domains for steady-state activation and inactivation (current availability), respectively. 5. Kinetics remained stable within a given neuron over the course of an experiment. However, considerable kinetic variation was exhibited from neuron to neuron, such that the half-times of activation and of inactivation spanned an order of magnitude. In all small neurons studied there appeared to be a singular kinetic component of the current, based on sensitivity to the conditioning potential, voltage dependence of activation, and inactivation half-time. 6. Unique closing properties were exhibited by Na+ channels of the small neurons. Hyperpolarization following a depolarization-induced fully inactivated state resulted in tail currents that appeared to be the consequence of reactivation of the slow Na+ conductance. Tail currents recorded at various times during a fixed level of depolarization revealed that the underlying channels accumulated into a volatile inactivated state over the course of the preceding depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Hyperpolarization-Activated Currents in the Growth Cone and Soma of Neonatal Rat Dorsal Root Ganglion Neurons in Culture

1997 ◽  
Vol 78 (1) ◽  
pp. 177-186 ◽  
Author(s):  
Z. Wang ◽  
R. J. Van Den Berg ◽  
D. L. Ypey
Keyword(s):  
Dorsal Root Ganglion ◽  
Growth Cone ◽  
Dorsal Root ◽  
Reversal Potential ◽  
Growth Cones ◽  
Dorsal Root Ganglion Neurons ◽  
Neonatal Rat ◽  
Midpoint Potential ◽  
Boltzmann Function ◽  
Ganglion Neurons

Wang, Z., R. J. Van Den Berg, and D. L. Ypey. Hyperpolarization-activated currents in the growth cone and soma of neonatal rat dorsal root ganglion neurons in culture. J. Neurophysiol. 78: 177–186, 1997. Dissociated dorsal root ganglion neuron growth cones and somata from neonatal rats were voltage and current clamped with the use of the perforated-patch whole cell configuration to study the occurrence and properties of slow hyperpolarization-activated currents ( I h) at both regions. Under voltage-clamp conditions I h, blockable by 2 mM extracellular CsCl, was present in 33% of the growth cones tested. Its steady-state activation as a function of voltage could be fitted with a single Boltzmann function with a midpoint potential of −97 mV. The time course of current activation could be best described by a double-exponential function. The magnitude of the fully activated conductance was 3.5 nS and the reversal potential amounted to −29 mV. At the soma, I h was found in 80% of the somata tested, which is much higher than occurrence at the growth cone. The steady-state activation curve of I h at the soma, fitted with a single Boltzmann function, had a midpoint potential of −92 mV, which was more positive than that in the growth cone. The double-exponential activation of the current was faster than in the growth cone. The fully activated conductance of 5.1 nS and the reversal potential of −27 mV were not significantly different from the values obtained at the growth cone. Membrane hyperpolarization by current-clamp pulses elicited depolarizing sags in 30% and 78% of the tested growth cones and somata, respectively, which is in agreement with our voltage-clamp findings. Termination of the hyperpolarizing current pulse evoked a transient membrane depolarization or an action potential at both sites. Application of 2 mM extracellular CsCl hyperpolarized the membrane potential reversibly by ∼5 mV and blocked the depolarizing sags and action potentials following the current injections at these regions. Thus I h contributes to the resting membrane potential and modulates the excitability of both the growth cone and the soma. Intracellular perfusion with the second messenger adenosine 3′,5′-cyclic monophosphate (cAMP) was only possible at the soma by the use of the conventional whole cell configuration. Addition of 100 μM cAMP to the pipette solution shifted the midpoint potential of the I h activation curve from −108 to −78 mV. The current activation time course was also accelerated. The reversal potential and the fully activated conductance underlying I h were not changed by cAMP. These results imply that cAMP primarily affects the gating kinetics of I h. Our results show for the first time quantitative differences in I h properties and occurrence at the growth cone and soma membrane. These differences may reflect differences in intracellular cAMP concentration and in the expression of I h.

Voltage-dependent Ca2+ currents in rat cardiac dorsal root ganglion neurons

2003 ◽  
Vol 961 (1) ◽  
pp. 171-178 ◽  
Author(s):  
Rafal Rola ◽  
P.J Szulczyk ◽  
Grzegorz Witkowski
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Dorsal Root Ganglion Neurons ◽  
Voltage Dependent ◽  
Ganglion Neurons
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