scholarly journals Ionic Basis of Tonic Firing in Spinal Substantia Gelatinosa Neurons of Rat

2004 ◽  
Vol 91 (2) ◽  
pp. 646-655 ◽  
Author(s):  
Igor V. Melnick ◽  
Sónia F. A. Santos ◽  
Karolina Szokol ◽  
Péter Szûcs ◽  
Boris V. Safronov
Keyword(s):  
Time Course ◽  
Substantia Gelatinosa ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Basic Pattern ◽  
Tonic Firing ◽  
Recovery From Inactivation ◽  
Ionic Conductances ◽  
Fast Activation

Ionic conductances underlying excitability in tonically firing neurons (TFNs) from substantia gelatinosa (SG) were studied by the patch-clamp method in rat spinal cord slices. Ca2+-dependent K+ (KCA) conductance sensitive to apamin was found to prolong the interspike intervals and stabilize firing evoked by a sustained membrane depolarization. Suppression of Ca2+ and KCA currents, however, did not abolish the basic pattern of tonic firing, indicating that it was generated by voltage-gated Na+ and K+ currents. Na+ and K+ channels were further analyzed in somatic nucleated patches. Na+ channels exhibited fast activation and inactivation kinetics and followed two-exponential time course of recovery from inactivation. The major K+ current was carried through tetraethylammonium (TEA)-sensitive rapidly activating delayed-rectifier (KDR) channels with a slow inactivation. The TEA-insensitive transient A-type K+ (KA) current was very small in patches and was strongly inactivated at resting potential. Block of KDR rather than KA conductance by 1 mM TEA lowered the frequency and stability of firing. Intracellular staining with biocytin revealed at least three morphological groups of TFNs. Finally, on the basis of present data, we created a model of TFN and showed that Na+ and KDR currents are sufficient to generate a basic pattern of tonic firing. It is concluded that the balanced contribution of all ionic conductances described here is important for generation and modulation of tonic firing in SG neurons.

Potassium current kinetics in bursting secretory neurons: effects of intracellular calcium

1991 ◽  
Vol 66 (5) ◽  
pp. 1455-1461 ◽  
Author(s):  
J. J. Martinez ◽  
C. G. Onetti ◽  
E. Garcia ◽  
S. Hernandez
Keyword(s):  
Steady State ◽  
Intracellular Calcium ◽  
Time Course ◽  
Membrane Potentials ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Patch Clamp Technique ◽  
Maximal Conductance ◽  
Whole Cell Patch Clamp

1. The kinetics of delayed rectifier (IK) and transient potassium (IA) currents and their modification by intracellular calcium ions in bursting X-organ neurons of the crayfish were studied with whole-cell patch-clamp technique. Activation and inactivation kinetics were analyzed according to Hodgkin and Huxley-type equations. 2. IK activates with sigmoidal time course at membrane potentials more positive than -38.4 +/- 3.5 (SD) mV (n = 5), and does not inactivate. The conductance through delayed rectifier channels (gK) is described by the equation gK = GKn2. 3. IA activates at membrane potentials close to the resting potential (-52.2 +/- 4.3 mV, n = 5) and, after a peak, inactivates completely. The conductance through A-channels (gA) can be described by the product of independent activation and inactivation parameters: gA = GAa4b. Both activation and inactivation processes are voltage and time dependent. 4. Steady-state activation of IK and IA as well as inactivation of IA can be described by Boltzmann distributions for single particles with valencies of 2.55 +/- 0.01 (n = 5), 1.60 +/- 0.25 (n = 5), and 3.87 +/- 0.39 (n = 3), respectively. 5. Increasing [Ca2+]i, we observed the following: 1) a considerable inactivation of IK during test pulses, 2) an increase of maximal conductance for IA, 3) a reduction of the valency of IA inactivation gating particle (from 3.87 to 2.27), 4) a reduction of the inactivation time constants of IA, and 5) a shift of the inactivation steady-state curve to more positive membrane potentials.(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of outward potassium currents in the action potentials of guinea pig ureteral myocytes

1997 ◽  
Vol 273 (3) ◽  
pp. C962-C972 ◽  
Author(s):  
J. L. Sui ◽  
C. Y. Kao
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Membrane Conductance ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Transient Outward Current ◽  
Delayed Rectifier Current ◽  
Fast Activation

Outward currents of freshly dissociated ureteral myocytes consist mainly of Ca(2+)-activated K+ current (IKCa) and a transient outward current (ITO). No delayed rectifier current was apparent. IKCa is small and nondecaying and fluctuates actively and irregularly. Blocking IKCa decreased resting membrane conductance and prolonged action potential plateaus, showing its roles in maintaining the resting potential and in repolarizing action potentials. It is also responsible for the membrane potential fluctuations on action potential plateaus. Neither 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate hydrochloride nor caffeine reduced the fluctuations in the outward current or in the action potentials, indicating that internal Ca2+ storage contributes little to the fluctuations. ITO has fast activation and inactivation kinetics with inactivation time constants of approximately 15 and 150 ms, respectively. Its highly negative voltage-availability relationship (V0.5 = -70.5 mV) suggests a low availability (< 5%) at normal resting potentials. It has only trivial effects on action potentials.

A delayed rectifier conductance in type I hair cells of the mouse utricle

1996 ◽  
Vol 76 (2) ◽  
pp. 995-1004 ◽  
Author(s):  
A. Rusch ◽  
R. A. Eatock
Keyword(s):  
Hair Cells ◽  
Time Course ◽  
Dissociation Constants ◽  
Resting Potential ◽  
Delayed Rectifier ◽  
Type I ◽  
Type Ii ◽  
Voltage Range ◽  
Average Maximum

1. Membrane currents of hair cells in acutely excised or cultured mouse utricles were recorded with the whole cell voltage-clamp method at temperatures between 23 and 36 degrees C. 2. Type I and II hair cells both had delayed rectifier conductances that activated positive to -55 mV. 3. Type I, but not type II, hair cells had an additional delayed rectifier conductance (gK,L) with an activation range that was unusually negative and variable. At 23-25 degrees C, V(1/2) values ranged from -88 to -62 mV in 57 cells. 4. gK,L was very large. At 23-25 degrees C, the average maximum chord conductance was 75 +/- 65 nS (mean +/- SD, n = 57; measured at -54 mV), or approximately 21 nS/pF of cell capacitance. 5. gK,L was highly selective for K+ over Na+ (permeability ratio PNa+/PK+:0.006), but unlike other delayed rectifiers, gK,L was significantly permeable to Cs+ (PCs+/PK+:0.31). gK,L was independent of extracellular Ca2+. 6. At -64 mV, Ba2+ and 4-aminopyridine blocked gK,L with apparent dissociation constants of 2.0 mM and 43 microM, respectively. Extracellular Cs+ (5 mM) blocked gK,L by 50% at -124 mV. Apamin (100 nM) and dendrotoxin (10 nM) has no effect. 7. The kinetic data of gK,L are consistent with a sequential gating model with at least two closed states and one open state. The slow activation kinetics (principal time constants at 23-25 degrees C:600-200 ms) had a thermal Q10 of 2.1. Inactivation (Q10:2.7) was partial at all temperatures. Deactivation followed a double-exponential time course and had a Q10 of 2.0. 8. At 23-25 degrees C, gK,L was appreciably activated at the mean resting potential of type I hair cells (-77 +/- 3.1 mV, n = 62), so that input conductances were often more than an order of magnitude larger than those of type II cells. If these conditions hold in vivo, type I cells would produce unusually small receptor potentials. Warming the cells to 36 degrees C produced parallel shifts in gK,L's activation range (0.8 +/- 0.3 mV/degrees C, n = 8), and in the resting potential (0.6 +/- 0.3 mV/degrees C, n = 4). Thus the high input conductances were not an artifact of unphysiological temperatures but remained high near body temperature. It remains possible that in vivo gK,L's activation range is less negative and input conductances are lower; the large variance in the voltage range of activation suggests that it may be subject to modulation.

Ultrarapid delayed rectifier current inactivation in human atrial myocytes: properties and consequences

1998 ◽  
Vol 275 (5) ◽  
pp. H1717-H1725 ◽  
Author(s):  
Jianlin Feng ◽  
Donghui Xu ◽  
Zhiguo Wang ◽  
Stanley Nattel
Keyword(s):  
Frequency Dependence ◽  
Time Course ◽  
Delayed Rectifier ◽  
Atrial Myocytes ◽  
Human Atrial Myocytes ◽  
Complete Inactivation ◽  
Delayed Rectifier Current ◽  
Recovery From Inactivation ◽  
Time Dependencies ◽  
Atrial Repolarization

The ultrarapid delayed rectifier current ( I K,ur) plays a significant role in human atrial repolarization and is generally believed to show little rate dependence because of slow and partial inactivation. This study was designed to evaluate in detail the properties and consequences of I K,urinactivation in isolated human atrial myocytes. I K,ur inactivated with a biexponential time course and a half-inactivation voltage of −7.5 ± 0.6 mV (mean ± SE), with complete inactivation during 50-s pulses to voltages positive to +10 mV (37°C). Recovery from inactivation proceeded slowly, with time constants of 0.42 ± 0.06 and 7.9 ± 0.9 s at −80 mV (37°C). Substantial frequency dependence was observed at 37°C over a clinically relevant range of frequencies. Inactivation was faster and occurred at more positive voltages at 37°C compared with room temperature. The voltage and time dependencies of Kv1.5 inactivation were studied in Xenopus oocytes to avoid overlapping currents and strongly resembled those of I K,ur in native myocytes. We conclude that, while I K,urinactivation is slow, it is extensive, and slow recovery from inactivation confers important frequency dependence with significant consequences for understanding the role of I K,ur in human atrial repolarization.

Phenotypic differences in transient outward K+ current of human and canine ventricular myocytes: insights into molecular composition of ventricular Ito

2004 ◽  
Vol 286 (2) ◽  
pp. H602-H609 ◽  
Author(s):  
Fadi G. Akar ◽  
Richard C. Wu ◽  
Isabelle Deschenes ◽  
Antonis A. Armoundas ◽  
Valentino Piacentino ◽  
...  
Keyword(s):  
Time Course ◽  
Ventricular Myocytes ◽  
Phenotypic Expression ◽  
Functional Expression ◽  
K Channel ◽  
Inactivation Kinetics ◽  
Phenotypic Properties ◽  
Interacting Protein ◽  
Phenotypic Differences ◽  
Recovery From Inactivation

The Ca2+-independent transient outward K+ current ( Ito) plays an important electrophysiological role in normal and diseased hearts. However, its contribution to ventricular repolarization remains controversial because of differences in its phenotypic expression and function across species. The dog, a frequently used model of human cardiac disease, exhibits altered functional expression of Ito. To better understand the relevance of electrical remodeling in dogs to humans, we studied the phenotypic differences in ventricular Ito of both species with electrophysiological, pharmacological, and protein-chemical techniques. Several notable distinctions were elucidated, including slower current decay, more rapid recovery from inactivation, and a depolarizing shift of steady-state inactivation in human vs. canine Ito. Whereas recovery from inactivation of human Ito followed a monoexponential time course, canine Ito recovered with biexponential kinetics. Pharmacological sensitivity to flecainide was markedly greater in human than canine Ito, and exposure to oxidative stress did not alter the inactivation kinetics of Ito in either species. Western blot analysis revealed immunoreactive bands specific for Kv4.3, Kv1.4, and Kv channel-interacting protein (KChIP)2 in dog and human, but with notable differences in band sizes across species. We report for the first time major variations in phenotypic properties of human and canine ventricular Ito despite the presence of the same subunit proteins in both species. These data suggest that differences in electrophysiological and pharmacological properties of Ito between humans and dogs are not caused by differential expression of the K channel subunit genes thought to encode Ito, but rather may arise from differences in molecular structure and/or posttranslational modification of these subunits.

Voltage-Gated Outward K Currents in Frog Saccular Hair Cells

2003 ◽  
Vol 90 (6) ◽  
pp. 3688-3701 ◽  
Author(s):  
Luigi Catacuzzeno ◽  
Bernard Fioretti ◽  
Fabio Franciolini
Keyword(s):  
Steady State ◽  
Hair Cells ◽  
Electrical Response ◽  
Quantitative Description ◽  
Delayed Rectifier ◽  
Kinetic Properties ◽  
Voltage Gated ◽  
Deactivation Kinetics ◽  
Recovery From Inactivation ◽  
Fast Activation

A biophysical analysis of the voltage-gated K (Kv) currents of frog saccular hair cells enzymatically isolated with bacterial protease VIII was carried out, and their contribution to the cell electrical response was addressed by a modeling approach. Based on steady-state and kinetic properties of inactivation, two distinct Kv currents were found: a fast inactivating IA and a delayed rectifier IDRK. IA exhibited a strongly hyperpolarized inactivation V1/2 (-83 mV), a relatively rapid single exponential recovery from inactivation (τrec of ∼100 ms at -100 mV), and fast activation and deactivation kinetics. IDRK showed instead a less-hyperpolarized inactivation V1/2 (-48 mV), a slower, double-exponential recovery from inactivation (τrec1 ∼ 490 ms and τrec2 ∼ 4,960 ms at -100 mV), and slower activation and deactivation kinetics. Steady-state activation gave a V1/2 and a k of -46.2 and 8.2 mV for IA and -48.3 and 4.2 mV for IDRK. Both currents were not appreciably blocked by bath application of 10 mM TEA, but were inhibited by 4-AP, with IDRK displaying a higher sensitivity. IDRK also showed a relatively low affinity to linopirdine, being half blocked at ∼50 μM. Steady-state and kinetic properties of IDRK and IA were described by 2nd- and 3rd-order Hodgkin–Huxley models, respectively. The goodness of our quantitative description of the Kv currents was validated by including IA and IDRK in a theoretical model of saccular hair cell electrical activity and by comparing the simulated responses with those obtained experimentally. This thorough description of the IDRK and IA will contribute toward understanding the role of these currents in the electrical response on this preparation.

Low-threshold, slow-inactivating Na+ potentials in the cockroach giant axon

1985 ◽  
Vol 54 (5) ◽  
pp. 1087-1100 ◽  
Author(s):  
H. Yawo ◽  
H. Kojima ◽  
M. Kuno
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Giant Axon ◽  
Resting Potential ◽  
Inactivation Kinetics ◽  
Na Channels ◽  
Slow Potential ◽  
Normal Medium ◽  
Plateau Potential ◽  
Low Threshold

Electrophysiological properties of the ventral giant axon in the abdominal nerve cord of the cockroach were studied by recording intracellular potentials following partial or complete block of the K+ conductance. When the K+ conductance was completely blocked by tetraethylammonium (TEA) and 3,4-diaminopyridine, the intensity of depolarizing currents necessary for eliciting the action potential was markedly decreased, and the action potential was followed by a prolonged plateau potential. During the plateau potential following the spike, the input resistance was significantly reduced. The plateau potential was not affected by changing the external Ca2+ concentration but depended on the external Na+ concentration in a manner expected from the Nernst equation and was blocked by tetrodotoxin (TTX). During the plateau potential, the Na+ conductance responsible for the spike was inactivated, whereas immediately after the plateau potential a newly evoked spike was not followed by a plateau potential, suggesting different inactivation kinetics between the spike and plateau Na+ conductances. When the K+ conductance was partially blocked by TEA alone, slow depolarizing responses were evoked at voltage levels a few millivolts more positive than the resting potential. The "threshold" for the slow potential was much lower than that for the spike potential. The slow potential produced after partial block of the K+ conductance was not affected by alterations of the external Ca2+ concentration but was blocked by TTX or in a Na+-free solution. Even in normal medium, a small TTX-sensitive depolarizing response was discernible. This response was similar in its time course and threshold to the slow potential observed after partial block of the K+ conductance. It is concluded that the cockroach giant axon has two populations of Na+ channels, which can be distinguished by differences in time course and voltage levels for activation and that the slow, low-threshold Na+-dependent potential is largely masked by delayed increases in the K+ conductance under normal conditions. It remains uncertain whether the low-threshold slow potential and the plateau potential originate from the same or different populations of Na+ channels.

scholarly journals A rapidly activating and slowly inactivating potassium channel cloned from human heart. Functional analysis after stable mammalian cell culture expression.

1993 ◽  
Vol 101 (4) ◽  
pp. 513-543 ◽  
Author(s):  
D J Snyders ◽  
M M Tamkun ◽  
P B Bennett
Keyword(s):  
Cell Lines ◽  
Time Course ◽  
Reversal Potential ◽  
Delayed Rectifier ◽  
Inactivation Kinetics ◽  
Constant Field ◽  
Slow Inactivation ◽  
Time Constants ◽  
K Concentration ◽  
External K

The electrophysiological properties of HK2 (Kv1.5), a K+ channel cloned from human ventricle, were investigated after stable expression in a mouse Ltk- cell line. Cell lines that expressed HK2 mRNA displayed a current with delayed rectifier properties at 23 degrees C, while sham transfected cell lines showed neither specific HK2 mRNA hybridization nor voltage-activated currents under whole cell conditions. The expression of the HK2 current has been stable for over two years. The dependence of the reversal potential of this current on the external K+ concentration (55 mV/decade) confirmed K+ selectivity, and the tail envelope test was satisfied, indicating expression of a single population of K+ channels. The activation time course was fast and sigmoidal (time constants declined from 10 ms to &lt; 2 ms between 0 and +60 mV). The midpoint and slope factor of the activation curve were Eh = -14 +/- 5 mV and k = 5.9 +/- 0.9 (n = 31), respectively. Slow partial inactivation was observed especially at large depolarizations (20 +/- 2% after 250 ms at +60 mV, n = 32), and was incomplete in 5 s (69 +/- 3%, n = 14). This slow inactivation appeared to be a genuine gating process and not due to K+ accumulation, because it was present regardless of the size of the current and was observed even with 140 mM external K+ concentration. Slow inactivation had a biexponential time course with largely voltage-independent time constants of approximately 240 and 2,700 ms between -10 and +60 mV. The voltage dependence of slow inactivation overlapped with that of activation: Eh = -25 +/- 4 mV and k = 3.7 +/- 0.7 (n = 14). The fully activated current-voltage relationship displayed outward rectification in 4 mM external K+ concentration, but was more linear at higher external K+ concentrations, changes that could be explained in part on the basis of constant field (Goldman-Hodgkin-Katz) rectification. Activation and inactivation kinetics displayed a marked temperature dependence, resulting in faster activation and enhanced inactivation at higher temperature. The current was sensitive to low concentrations of 4-aminopyridine, but relatively insensitive to external TEA and to high concentrations of dendrotoxin. The expressed current did not resemble either the rapid or the slow components of delayed rectification described in guinea pig myocytes. However, this channel has many similarities to the rapidly activating delayed rectifying currents described in adult rat atrial and neonatal canine epicardial myocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Rapid recovery from K current inactivation on membrane hyperpolarization in molluscan neurons.

1984 ◽  
Vol 84 (6) ◽  
pp. 861-875 ◽  
Author(s):  
P Ruben ◽  
S Thompson
Keyword(s):  
Time Course ◽  
Outward Current ◽  
Rapid Recovery ◽  
Resting Potential ◽  
Molluscan Neurons ◽  
Membrane Hyperpolarization ◽  
Time Constants ◽  
Recovery From Inactivation ◽  
Voltage Dependent ◽  
K Current

Recovery from K current inactivation was studied in molluscan neurons using two-microelectrode and internal perfusion voltage clamps. Experiments were designed to study the voltage-dependent delayed outward current (IK) without contamination from other K currents. The amount of recovery from inactivation and the rate of recovery increase dramatically when the membrane potential is made more negative. The time course of recovery at the resting potential, -40 mV, is well fit by a single exponential with a time constant of 24.5 s (n = 7). At more negative voltages, the time course is best fit by the sum of two exponentials with time constants at -90 mV of 1.7 and 9.8 s (n = 7). In unclamped cells, a short hyperpolarization can cause rapid recovery from inactivation that results in a shortening of the action potential duration. We conclude that there are two inactivated states of the channel and that the time constants for recovery from both states are voltage dependent. The results are discussed in terms of the multistate model for K channel gating that was developed by R. N. Aldrich (1981, Biophys. J., 36:519-532).

scholarly journals Canine Myocytes Represent a Good Model for Human Ventricular Cells Regarding Their Electrophysiological Properties

2021 ◽  
Vol 14 (8) ◽  
pp. 748
Author(s):  
Péter P. Nánási ◽  
Balázs Horváth ◽  
Fábián Tar ◽  
János Almássy ◽  
Norbert Szentandrássy ◽  
...  
Keyword(s):  
Action Potential ◽  
Time Course ◽  
Laboratory Animals ◽  
Delayed Rectifier ◽  
Ion Currents ◽  
Human Cardiomyocytes ◽  
Ventricular Cells ◽  
Repolarization Reserve ◽  
Electrophysiological Studies ◽  
K Current

Due to the limited availability of healthy human ventricular tissues, the most suitable animal model has to be applied for electrophysiological and pharmacological studies. This can be best identified by studying the properties of ion currents shaping the action potential in the frequently used laboratory animals, such as dogs, rabbits, guinea pigs, or rats, and comparing them to those of human cardiomyocytes. The authors of this article with the experience of three decades of electrophysiological studies, performed in mammalian and human ventricular tissues and isolated cardiomyocytes, summarize their results obtained regarding the major canine and human cardiac ion currents. Accordingly, L-type Ca2+ current (ICa), late Na+ current (INa-late), rapid and slow components of the delayed rectifier K+ current (IKr and IKs, respectively), inward rectifier K+ current (IK1), transient outward K+ current (Ito1), and Na+/Ca2+ exchange current (INCX) were characterized and compared. Importantly, many of these measurements were performed using the action potential voltage clamp technique allowing for visualization of the actual current profiles flowing during the ventricular action potential. Densities and shapes of these ion currents, as well as the action potential configuration, were similar in human and canine ventricular cells, except for the density of IK1 and the recovery kinetics of Ito. IK1 displayed a largely four-fold larger density in canine than human myocytes, and Ito recovery from inactivation displayed a somewhat different time course in the two species. On the basis of these results, it is concluded that canine ventricular cells represent a reasonably good model for human myocytes for electrophysiological studies, however, it must be borne in mind that due to their stronger IK1, the repolarization reserve is more pronounced in canine cells, and moderate differences in the frequency-dependent repolarization patterns can also be anticipated.

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