Role in neuronal cell migration for high-threshold potassium currents in the chicken hindbrain
47
Citation
33
Reference
10
Related Paper
Citation Trend
Abstract:
We have investigated the influence of voltage-dependent, potassium conductances on the migration of embryonic neurons, using a culture preparation taken from the acoustico-vestibular anlage long before the onset of electrical excitability and synaptic function. Whole-cell patch clamp recordings from migrating neuroblasts at Hamburger-Hamilton stage 28 (E 5.5) revealed the exclusive expression of voltage-dependent, high-threshold, outward currents, activating at potentials positive to -20 mV. These currents were completely suppressed by the potassium channel blockers, 1.0 mM tetraethylammonium chloride (TEA) or 1.0 mM 4-aminopyridine (4-AP). In control media, the active migration of individual neuroblasts was recorded at 27 ± 6 μm per hr. Within minutes after adding either drug to the culture, normal migration completely stopped for several hours. Calcium channel blockers, ω-conotoxin (3 μM) or cadmium chloride (100 μM), slowed, but did not halt, migration, while nickel chloride (100 μM) or N-methyl-D-glucamine (1 mM) had no effect. However, within 8 hr after TEA exposure, migratory activity usually returned. This recovery was associated with the appearance of a previously undetected, low-threshold and 4-AP- sensitive potassium conductance. We suggest that high-threshold, TEA/4-AP-sensitive potassium channels may normally support the migration of these neurons, while their chronic blockade can be compensated by the appearance of novel potassium channels. Potassium currents may act in concert with N-type calcium channels to regulate neuronal migration. J. Neurosci. Res. 58:805–814, 1999. © 1999 Wiley-Liss, Inc.Keywords:
Tetraethylammonium chloride
Potassium channel blocker
Tetraethylammonium
4-Aminopyridine
the present study was undertaken to evaluate [ca 2+ ] i signals that occur in human sperm cells exposed in vitro to three diverse compounds; progesterone, 4-aminopyridine (a highly effective inducer of hyperactivation in human sperm) and tetraethylammonium.the [ca 2+ ] i reached after the extracellular calcium treatment was always higher in normozoospermic samples pretreated with progesterone than in pathozoospermic samples pretreated with progesterone.there were no changes in calcium signal in spermatozoa pretreated with progesterone from patients with oligozoospermia and leucocytospermia compared to control samples (without progesterone).[ca 2+ ] i .was always higher in pathozoospermic samples without 4-aminopyridine and always lower in pathozoospermic samples with 4-aminopyridine compared to these values in normozoospermic men. the 2 mM extracellular calcium administration to spermatozoa pretreated with tetraethylammonium did not result in a detectable increase in [ca 2+ ] i in normo-and pathozoospermic samples.the mechanisms of progesterone-dependent activation of the ca 2+ -entry and the functioning of the voltage gated ca 2+ -channels of plasmalemma are disturbed in pathologies -there was no increase in the ca 2+ level in the conditions of k + -depolarization (in the presence of inhibitors of k + -channels).k e y w o r d s: calcium, spermatozoa, progesterone, inhibitors of k + channels.
4-Aminopyridine
Tetraethylammonium
Potassium channel blocker
2-Aminopyridine
Cite
Citations (0)
Sheep somatotroph-enriched cultures were obtained by means of enzyme dissociation and Percoll gradient separation. Nystatin-perforated-whole-cell recordings were performed on post-recording-identified somatotrophs after 4–14 days in vitro. Using Ca2+-free, tetrodotoxin-containing (1 µM) bath solution and K+ electrode solution, three types of voltage-dependent K+ currents were recorded as inward rectifying, outward transient and outward delayed rectifying K+ currents. The inward rectifying K+ current was very small at physiological extracellular K+ concentrations (5 mM) and enhanced by increasing the K+ concentration in the bath to 55 mM; it was blocked by tetraethylammonium (2 mM) but not by 4-aminopyridine (5 mM). A transient outward K+ current appeared at –50 mV and was selectively diminished by 4-aminopyridine (2 or 4 mM). A delayed rectifying outward K+ current was observed when the membrane potential was depolarized to -20 mV and was blocked by tetraethylammonium (2 mM) but not 4-aminopyridine (4 mM). Application of 4-aminopyridine but not tetraethylammonium (up to 5 mM) depolarized the cell membrane potential recorded under current clamp conditions and triggered action potentials when the bath solution contained Ca2+ (2 mM) but not tetrodotoxin. The intracellular Ca2+ concentration was increased by 4-aminopyridine as was growth hormone release. Therefore, the 4-aminopyridine-sensitive transient outward K+ current appears to be important in the determining the resting potential of ovine somatotrophs and plays a major role in regulating basal intracellular Ca2+ concentration and growth hormone secretion.
Tetraethylammonium
4-Aminopyridine
Tetrodotoxin
Tetraethylammonium chloride
Percoll
Cite
Citations (47)
Previous investigations have demonstrated that compounds capable of blocking presynaptic potassium channels can stimulate neurotransmitter release at both peripheral and central synapses. This study examined the in vitro effects of the "classical" potassium channel blockers 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the spontaneous basal release of [3H]5-hydroxytryptamine ([3H]5-HT) from rat hippocampal slices using an automated superfusion apparatus. 4-AP and structural analogs increased the spontaneous basal release of [3H]5-HT in a concentration-related manner. The rank order of potencies from the estimated EC50 values indicated that 3,4-diaminopyridine (0.88 mM) approximately 4-AP (1.2 mM) > 2-AP (89 mM) > 3-AP (100 mM) > pyridine (256 mM). TEA stimulated [3H]5-HT release with an estimated EC50 value of 63 mM and was less efficacious than the pyridine congeners. The enhancement of release induced by 1 mM 4-AP was additive with 100 mM TEA and 5 microM veratridine but not with 3,4-diaminopyridine or KCl (25 and 50 mM). The release induced by 4-AP (0.3, 1 and 10 mM) and TEA (30, 100 and 300 mM) was significantly attenuated in a calcium-free buffer containing 1 mM ethylene glycol-bis(b-aminoethyl ether N,N,N',N'-tetraacetic acid. Tetrodotoxin (1 microM), a sodium channel blocker, was unable to block the response to 4-AP (1 mM) and TEA (100 mM). Notably, this concentration of tetrodotoxin reduced the stimulation of [3H]5-HT release produced by the sodium channel opener veratridine (5 microM). Taken together, the results demonstrate that potassium channel blockade can enhance the spontaneous basal release of [3H]5-HT in rat hippocampal slices. These effects are at least partly dependent on extracellular calcium and do not appear to be mediated by modulating sodium channel function.
Veratridine
Tetraethylammonium
Tetrodotoxin
4-Aminopyridine
Potassium channel blocker
Channel blocker
Cite
Citations (48)
4-Aminopyridine
Tetraethylammonium
Potassium channel blocker
Cite
Citations (0)
Tetraethylammonium
4-Aminopyridine
Afterhyperpolarization
Potassium channel blocker
Hyperpolarization
Tetraethylammonium chloride
Cite
Citations (79)
1. The relationship between ionic current inactivation and immobilization of ‘off'‐gating charge in human Kv1.5 channels expressed in human embryonic kidney (HEK293) cells was studied using 4‐aminopyridine (4‐AP) and tetraethylammonium chloride (TEA‐Cl). 2. The charge transferred during short (< 10 ms) depolarizations (Q(on)) was conserved on repolarization (Q(off)) although peak off‐gating current (off‐Ig) was reduced and the time course prolonged (tau decay increased from 0.4 to > 1.2 ms). For +80 mV pulses longer than 50 ms, Q(off) at 20 ms was less than Q(on) (Q(off)/Q(on) ratio was 0.26 +/‐ 0.06 at 450 ms). We attribute this to a relative ‘immobilization’ of gating charge during long depolarizations. 3. 4‐AP (0.1‐1 mM) prevented slowing of off‐Ig, allowing saturation of peak off‐Ig. 4‐AP also completely prevented immobilization of off‐Ig after long depolarizations. In 1 mM 4‐AP, off‐Ig waveforms decayed rapidly and the charge ratio Q(off)/Q(on) remained at 1.0. 4. In addition to its effects on Ig, 1 mM 4‐AP prevented the slow inactivation of ionic current seen during strong depolarizations. An initial block was caused by 4‐AP or 1 mM intracellular TEA internally applied. However, only 4‐AP prevented the slower, later development of C‐type inactivation. 5. We suggest that slow current inactivation is accompanied by a gating charge immobilization in Kv1.5. 4‐AP potently inhibits the changes in Q(off)/Q(on0, off‐Ig, and ionic currents that underlie slow inactivation. Some actions of 4‐AP appear independent of its properties as a blocker of open K+ channels, and are not mimicked by internal TEA.
4-Aminopyridine
Tetraethylammonium chloride
Tetraethylammonium
Potassium channel blocker
HEK 293 cells
Cite
Citations (42)
Tetraethylammonium
Tetraethylammonium chloride
Potassium channel blocker
Channel blocker
Cite
Citations (2)
Tetraethylammonium chloride
Tetraethylammonium
4-Aminopyridine
Cite
Citations (5)
The effects of 4‐aminopyridine (4‐AP) and tetraethylammonium (TEA) on the outward potassium currents in the rapidly and slowly adapting stretch receptor neurons (SRNs) of the crayfish ( Pacifastacus leniusculus ) were studied using a two micro‐electrode voltage‐clamp technique. The leakage current was not affected by either 4‐AP or TEA. External 4‐AP blocked the peak outward current in a dose‐dependent manner (1:1 stoichiometry) with an apparent dissociation constant ( K d ) of 2.3 ± 0.2 mm (mean ± SEM) in the slowly and 1.4 ± 0.2 mm in the rapidly adapting SRN, the block being voltage dependent. External application of TEA resulted in a block of the steady state current enhancing the transient characteristics of the current response. The block appeared to deviate from a 1: 1 stoichiometry and the apparent K d for TEA was 9.6 ± 3.4 mm with a cooperativity factor n = 0.43 ± 0.03 in the slowly adapting SRN and 34.5 ± 9.2 mm and 0.37 ± 0.03 respectively in the rapidly adapting SRN. Low Ca 2+ , apamin and charybdotoxin, which are known to block Ca 2+ ‐dependent K‐currents, had no effects on the outward current as was also the case with catechol. It is concluded that the different effects of TEA and 4‐AP on the outward current in the two types of SRNs can be explained by the presence of at least two, probably heteromultimeric, channel populations having similar sensitivity to 4‐AP but different sensitivity to TEA. One channel has a high affinity ( K d = 0.8–1.6 mm) for TEA and the other a low affinity ( K d = 173–213 mm) for TEA. The low‐affinity channel seems to dominate in the slowly adapting SRN while both channels are equally common in the rapidly adapting SRN. Further, the present results do not support the existence of a macroscopic Ca 2+ ‐dependent K + current in the SRNs.
4-Aminopyridine
Tetraethylammonium
Apamin
Tetraethylammonium chloride
Potassium channel blocker
Tetrodotoxin
Cite
Citations (22)
1 Cat splenic slices prelabelled with [3H]-noradrenaline were incubated in oxygenated Krebs-bicarbonate solution at 37°C, and the spontaneous total 3H release into different incubation media monitored. In normal Krebs bicarbonate solution, the spontaneous tritium fractional release amounted to 3.7% of the tissue radiactivity content per 5 min collection period. 2 Tetraethylammonium (TEA) increased spontaneous transmitter release in a concentration-dependent manner; the release was maximal at 30 mm and was 3.5 times the basal release. 3 4-Aminopyridine (4-AP) also enhanced the spontaneous release of tritium. The response increased linearly with 4-AP concentration (1–10 mm). With 10 mm 4-AP, the release was as much as 6 times the basal transmitter release. Guanidine was much less potent than either TEA or 4-AP. 4 The secretory response to TEA or 4-AP was little affected by changes in external Ca2+, Mg2+, Na+, Cl−, H2PO4− or by tetrodotoxin. 5 However, transmitter release evoked by TEA or 4-AP strongly depended upon the concentration of HCO3− of the incubation solution; in fact, the secretory response varied almost linearly between 1 and 25 mm HCO3−. 6 The mechanisms underlying these effects are probably related to the well-known ability of TEA and 4-AP to block K+ conductance that would cause depolarization of the splenic sympathetic nerve terminals. The HCO3− requirements for the secretory response are probably related to the ability of CO2/HCO3− solutions to mobilize and release Ca2+ from intracellular organelles.
Tetraethylammonium
4-Aminopyridine
Bicarbonate
Tetraethylammonium chloride
Tetrodotoxin
Cite
Citations (6)