Benzolamide inhibits low-threshold calcium currents in hippocampal pyramidal neurons

1995 ◽  
Vol 74 (6) ◽  
pp. 2774-2777 ◽  
Author(s):  
J. A. Gottfried ◽  
M. Chesler
Keyword(s):  
Carbonic Anhydrase ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Ca Currents

1. Benzolamide is a poorly permeant sulfonamide inhibitor of the enzyme carbonic anhydrase. We studied the effect of benzolamide on low-threshold (LT) Ca currents in neonatal hippocampal CAl neurons. 2. In hippocampal slices, benzolamide (2-10 microM) inhibited the LT current 30-75% in voltage-clamped CAl pyramidal cells (n = 6). In slices bathed in N-2-hydroxypiperazine-N'-2-ethane-sulfonic acid (HEPES)-buffered Ringer, benzolamide also reduced the LT current, indicating that the action of the drug was not bicarbonate dependent. 3. Benzolamide inhibited LT Ca currents 20-75% in acutely dissociated CAl neurons in HEPES (n = 18): inhibition was 36 +/- 8% (mean +/- SE; n = 7) and 50 +/- 8% (n = 7) at 10 and 50 microM benzolamide, respectively. By contrast, high-threshold calcium currents recorded in CAl pyramidal cells (n = 18) and dorsal root ganglion neurons (n = 4) were virtually unaffected by benzolamide. 4. These results indicate that benzolamide inhibits LT Ca channels in central neurons and suggest caution in the use of this agent to inhibit extracellular carbonic anhydrase in excitable tissues.

Calcium currents in acutely isolated human neocortical neurons

1993 ◽  
Vol 69 (5) ◽  
pp. 1596-1606 ◽  
Author(s):  
R. J. Sayer ◽  
A. M. Brown ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Pyramidal Neurons ◽  
Intractable Epilepsy ◽  
Pyramidal Cells ◽  
Cell Voltage ◽  
Threshold Current ◽  
Calcium Currents ◽  
High Threshold ◽  
Peak Current ◽  
Neocortical Neurons ◽  
Low Threshold

1. Ca2+ currents were investigated in neurons acutely isolated from adult human temporal neocortex. The aim was to compare the basic characteristics of the currents with those previously described in animals and to examine the effects of dihydropyridine Ca2+ antagonists and antiepileptic drugs. The tissue, obtained from patients undergoing temporal lobe surgery for medically intractable epilepsy, was sliced, incubated in papain, and triturated. 2. Most of the isolated neurons (34 of 36) were judged to be pyramidal cells by their morphology. Whole-cell voltage-clamp recordings revealed two components of Ca2+ current: 1) a low-threshold (T-type) current that was transient, small in amplitude, and required hyperpolarization more negative than -70 mV for removal of inactivation and 2) a high-threshold current that was slowly inactivating and was available for activation from more positive potentials. The characteristics of the Ca2+ currents were very similar to those in the neocortical neurons of young rats, although the low-threshold current was less prominent in the human cells. 3. Subcomponents of the high-threshold current were identified by pharmacology. About 20% of the peak current was blocked by omega-conotoxin GVIA (presumed N current) and 40-50% of the peak current was blocked by micromolar concentrations of the dihydropyridine Ca2+ antagonists nifedipine and nimodipine (presumed L current). In two neurons tested with a range of nimodipine concentrations, the threshold for suppression of the high-threshold current was approximately 10 nM. 4. The antiepileptic agents ethosuximide, carbamazepine, and valproate did not affect the Ca2+ currents at therapeutically relevant concentrations. Phenytoin marginally reduced the low- and high-threshold Ca2+ currents at 8 microM (a concentration corresponding to the upper therapeutic range). The results do not support the hypothesis that inhibition of Ca2+ currents in neocortical pyramidal neurons is a major action of these drugs.

Modulation of Voltage-Activated Calcium Currents by Mechanical Stimulation in Rat Sensory Neurons

1998 ◽  
Vol 80 (4) ◽  
pp. 1647-1652 ◽  
Author(s):  
Yona Bouskila ◽  
Hugh Bostock
Keyword(s):  
Action Potential ◽  
Sensory Neurons ◽  
Mechanical Stimulation ◽  
Action Potential Duration ◽  
Calcium Currents ◽  
Dorsal Root Ganglion Neurons ◽  
Patch Clamp Technique ◽  
Whole Cell Patch Clamp ◽  
Low Threshold ◽  
Ganglion Neurons

Bouskila, Yona and Hugh Bostock. Modulation of voltage-activated calcium currents by mechanical stimulation in rat sensory neurons. J. Neurophysiol. 80: 1647–1652, 1998. We examined the effects of mechanical stress, induced by a stream of bath solution, on evoked action potentials, electrical excitability, and Ca2+ currents in rat dorsal root ganglion neurons in culture with the use of the whole cell patch-clamp technique. Action-potential duration was altered reversibly by flow in 39% of the 51 neurons tested, but membrane potential and excitability were unaffected. The flow-induced increases and decreases in action-potential duration were consistent with the different effects of flow on two types of Ca2+ channel, determined by voltage-clamp recordings of Ba2+ currents. Current through ω-conotoxin–sensitive (N-type) Ca2+ channels increased by an estimated 74% with flow, corresponding to 23% increase in the total high voltage–activated current, whereas current through low-threshold voltage-activated (T-type) channels decreased by 14%. We conclude that modulation of voltage-activated Ca2+ currents constitutes a route by which mechanical events can regulate Ca2+ influx in sensory neurons.

Pre- and Postsynaptic Activation of M-Channels By a Novel Opener Dampens Neuronal Firing and Transmitter Release

2007 ◽  
Vol 97 (1) ◽  
pp. 283-295 ◽  
Author(s):  
Asher Peretz ◽  
Anton Sheinin ◽  
Cuiyong Yue ◽  
Nurit Degani-Katzav ◽  
Gilad Gibor ◽  
...  
Keyword(s):  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Critical Role ◽  
Hippocampal Slices ◽  
Gaba Release ◽  
Neuronal Firing ◽  
Dorsal Root Ganglion Neurons ◽  
Postsynaptic Currents ◽  
M Channels ◽  
Ganglion Neurons

The M-type K+ current (M-current), encoded by Kv7.2/3 (KCNQ2/3) K+ channels, plays a critical role in regulating neuronal excitability because it counteracts subthreshold depolarizations. Here we have characterized the functions of pre- and postsynaptic M-channels using a novel Kv7.2/3 channel opener, NH6, which we synthesized as a new derivative of N-phenylanthranilic acid. NH6 exhibits a good selectivity as it does not affect Kv7.1 and IKS K+ currents as well as NR1/NR2B, AMPA, and GABAA receptor-mediated currents. Superfusion of NH6 increased recombinant Kv7.2/3 current amplitude (EC50 = 18 μM) by causing a hyperpolarizing shift of the voltage activation curve and by markedly slowing the deactivation kinetics. Activation of native M-currents by NH6 robustly reduced the number of evoked and spontaneous action potentials in cultured cortical, hippocampal and dorsal root ganglion neurons. In hippocampal slices, NH6 decreased somatically evoked spike afterdepolarization of CA1 pyramidal neurons and induced regular firing in bursting neurons. Activation of M-channels by NH6, potently reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents. Activation of M-channels also decreased the frequency of miniature excitatory (mEPSC) and inhibitory (mIPSC) postsynaptic currents without affecting their amplitude and waveform, thus suggesting that M-channels presynaptically inhibit glutamate and GABA release. Our results suggest a role of presynaptic M-channels in the release of glutamate and GABA. They also indicate that M-channels act pre- and postsynaptically to dampen neuronal excitability.

Agonists for neuropeptide Y receptor subtypes NPY-1 and NPY-2 have opposite actions on rat nodose neuron calcium currents

1993 ◽  
Vol 70 (1) ◽  
pp. 324-330 ◽  
Author(s):  
J. W. Wiley ◽  
R. A. Gross ◽  
R. L. MacDonald
Keyword(s):  
Neuropeptide Y ◽  
Calcium Current ◽  
Calcium Currents ◽  
Peak Amplitude ◽  
High Threshold ◽  
Receptor Subtypes ◽  
Patch Clamp Technique ◽  
Voltage Dependent ◽  
Low Threshold ◽  
Ganglion Neurons

1. The whole-cell variation of the patch-clamp technique was used to study the effect of neuropeptide Y (NPY) and preferential agonists for the NPY-1 and NPY-2 receptor subtypes on voltage-dependent calcium currents in acutely dissociated postnatal rat nodose ganglion neurons. 2. Both low- and high-threshold calcium current components were present. NPY altered voltage-dependent calcium currents in approximately 50% of neurons studied. NPY (0.1-100 nM, ED50 6 nM) decreased the peak amplitude of transient high-threshold calcium currents in approximately 45% of the neurons. NPY (100 nM) decreased the peak amplitude of these currents 31 +/- 5% (mean +/- SE). However, in approximately 5% of the neurons NPY (100 nM) caused a reversible and reproducible increase in transient high-threshold calcium currents of 21 +/- 4%. NPY did not affect either transient low-threshold or slowly inactivating high-threshold calcium current components. 3. Application of the C-terminal fragment NPY 13-36 (100 nM), a preferential agonist for NPY-2 receptors, reversibly decreased the peak amplitude of transient high-threshold calcium currents by 26 +/- 5% in 9 of 20 cells (45%). Application of [Pro34]-NPY (100 nM), a preferential agonist for NPY-1 receptors, reversibly increased the peak amplitude of transient high-threshold calcium currents 20 +/- 4% in 23 out of 48 neurons (48%). Six of 20 neurons (30%) responded to application of both agonists. Neither the NPY-1 nor NPY-2 agonists affected transient low-threshold or slowly inactivating high-threshold calcium current components.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Low-Threshold, Persistent Sodium Current in Rat Large Dorsal Root Ganglion Neurons in Culture

1997 ◽  
Vol 77 (3) ◽  
pp. 1503-1513 ◽  
Author(s):  
Mark D. Baker ◽  
Hugh Bostock
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Sodium Current ◽  
Threshold Current ◽  
Persistent Current ◽  
Dorsal Root Ganglion Neurons ◽  
High Threshold ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Large Neurons

Baker, Mark D. and Hugh Bostock. Low-threshold, persistent sodium current in rat large dorsal root ganglion neurons in culture. J. Neurophysiol. 77: 1503–1513, 1997. Dorsal root ganglion neurons from adult rats (≥200 g) were maintained in culture for between 1 and 3 days. Membrane currents generated by large neurons (50–75 μm apparent diameter) were recorded with the whole cell patch-clamp technique. Large neurons generated transient Na+ currents and at least two types of inward current that persisted throughout 200-ms voltage-clamp steps to +20 mV. One persistent current activated close to −35 mV (high threshold), whereas in about half of the cells another persistent current began to activate negative to −70 mV (low threshold). The high-threshold persistent current was identified as a Ca2+ current, as previously described in these neurons. The low-threshold current was reversibly suppressed either by replacing external Na+ with tetramethylammonium ions or by reducing external Na+ concentration ([Na+]) and simultaneously raising external [Ca2+]. It was blocked by tetrodotoxin (TTX) with an apparent equilibrium dissociation constant in the single nanomolar range. We conclude that the low-threshold current is a TTX-sensitive, persistent Na+ current. The persistent TTX-sensitive current contributed to steady-state membrane current from at least −70 mV to 0 mV, a wider potential range than predicted by activation-inactivation gating overlap for transient Na+ current. Because of its low threshold and fast activation kinetics, the persistent Na+ current is expected to play an important role in determining membrane excitability.

Intracellular QX-314 inhibits calcium currents in hippocampal CA1 pyramidal neurons

1996 ◽  
Vol 76 (3) ◽  
pp. 2120-2124 ◽  
Author(s):  
M. J. Talbot ◽  
R. J. Sayer
Keyword(s):  
Pyramidal Neurons ◽  
Pyramidal Cells ◽  
Calcium Currents ◽  
High Threshold ◽  
Chloride Salt ◽  
Ca1 Pyramidal Cells ◽  
Na Currents ◽  
Hippocampal Ca1 ◽  
And Control ◽  
In Cells

1. The effects of intracellular QX-314 on Ca2+ currents were examined in CA1 pyramidal cells acutely isolated from rat hippocampus. In neurons dialyzed with 10 mM QX-314 (bromide salt), the amplitude of the high-threshold Ca2+ current was on average 20% of that in control cells and the current-voltage relationships (I-Vs) were shifted in the positive voltage direction. 2. The positive shift in the I-Vs was due to the presence of intracellular Br-, because it was reproduced by 10 mM NaBr and was not present when the chloride salt of QX-314 was used. 3. Low-threshold (T-type) Ca2+ currents, at test voltages of -50 and -40 mV, were on average < 45% of control amplitude in cells containing 10 mM QX-314 (chloride salt) and < 10% of control amplitude in cells with 10 mM QX-314 (bromide salt). 4. In neurons dialyzed with 1 mM QX-314, high-threshold Ca2+ currents were still significantly different from control and Na+ currents were not completely blocked. 5. The proportions of high-threshold Ca2+ current blocked by omega-conotoxin GVIA, omega-agatoxin IVA, and nimodipine were similar in cells dialyzed with 10 mM QX-314 and control cells, indicating that the drug does not selectively inhibit any of the Ca2+ channel subtypes distinguished by these antagonists.

Metabotropic glutamate receptor-mediated suppression of L-type calcium current in acutely isolated neocortical neurons

1992 ◽  
Vol 68 (3) ◽  
pp. 833-842 ◽  
Author(s):  
R. J. Sayer ◽  
P. C. Schwindt ◽  
W. E. Crill
Keyword(s):  
Glutamate Receptor ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
High Threshold ◽  
External Application ◽  
Metabotropic Glutamate ◽  
Neocortical Neurons ◽  
Old Rats ◽  
Low Threshold ◽  
Ca2 Channels

1. The effects of metabotropic glutamate receptor (mGluR) stimulation on whole-cell Ca2+ currents were studied in pyramidal neurons isolated from the dorsal frontoparietal neocortex of rat. The selective mGluR agonist cis-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid [trans-ACPD (100 microM)] suppressed the peak high-threshold Ca2+ current by 21 +/- 1.7% (mean +/- SE) in 40 of 43 cells from 10- to 21-day-old rats. Consistent with previous findings for mGluR, glutamate, quisqualate, and ibotenate [but not alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)] reduced the Ca2+ currents, and the responses were not blocked by the ionotropic glutamate receptor antagonists 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) and DL-2-amino-5-phosphonovaleric acid (APV). EC50S for Ca2+ current suppression were 29 nM for quisqualate, 2.3 microM for glutamate, and 13 microM for trans-ACPD. 2. The low-threshold Ca2+ current was not modulated by trans-ACPD. The component of the high-threshold CA2+ current suppressed by mGluR was determined by pharmacology; the responses were not affected by omega-conotoxin GVIA but were occluded by the dihydropyridine Ca2+ antagonist nifedipine. Ca2+ tail currents prolonged by the dihydropyridine Ca2+ agonist (+)-SDZ 202-79] were suppressed by mGluR stimulation in parallel with the peak current. These findings strongly suggest that L-type Ca2+ channels are modulated by mGluR. 3. In neurons dialyzed with 100 microM guanosine 5'-(gamma-thio)triphosphate (GTP-gamma-S), Ca2+ current suppression was elicited by the first application of trans-ACPD (in 5 of 6 cells), but not by subsequent applications. Responses in neurons dialyzed with 2 mM guanosine 5'-(beta-thio)diphosphate (GDP-beta-S) were significantly smaller than controls. The results are consistent with mGluR acting via linkage to a G protein. 4. The responses to mGluR agonists were smaller when the external Ca2+ was replaced by Ba2+, indicating that some part of the mechanism underlying the current suppression is Ca2+ dependent. Because mGluR stimulates phosphoinositide turnover and release of Ca2+ from intracellular stores in other types of neurons, the possibility of released Ca2+ mediating inactivation of Ca2+ channels was considered. However, the Ca2+ current suppression was not attenuated by strong intracellular Ca2+ buffering [20 mM bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)], by dialysis with 100 microM inositol-1,4,5-triphosphate (IP3), or by external application of 1 microM thapsigargin. 5. We conclude that in neocortical neurons, one action of mGluR is to suppress the component of high-threshold Ca2+ current conducted by L-type Ca2+ channels.(ABSTRACT TRUNCATED AT 400 WORDS)

5HT Increases Excitability of Nociceptor-Like Rat Dorsal Root Ganglion Neurons Via cAMP-Coupled TTX-Resistant Na+Channels

2001 ◽  
Vol 86 (1) ◽  
pp. 241-248 ◽  
Author(s):  
Luz M. Cardenas ◽  
Carla G. Cardenas ◽  
Reese S. Scroggs
Keyword(s):  
Dorsal Root Ganglion ◽  
Signaling Pathway ◽  
Dorsal Root ◽  
Phosphodiesterase Inhibitor ◽  
Dorsal Root Ganglion Neurons ◽  
Receptor Coupling ◽  
Low Threshold ◽  
Ganglion Neurons ◽  
Serotonergic Modulation

The physiological effects of 5HT receptor coupling to TTX-resistant Na+ current, and the signaling pathway involved, was studied in a nociceptor-like subpopulation of rat dorsal root ganglion (DRG) cells (type 2), which can be identified by expression of a low-threshold, slowly inactivating A-current. The 5HT-mediated increase in TTX-resistant Na+ current in type 2 DRG cells was mimicked and occluded by 10 μM forskolin. Superfusion of type 2 DRG cells on the outside with 1 mM 8-bromo-cAMP or chlorophenylthio-cAMP (CPT-cAMP) increased the Na+ current, but less than 5HT itself. However, perfusion of the cells inside with 2 mM CPT-cAMP strongly increased the amplitude of control Na+currents and completely occluded the effect of 5HT. Thus it appears that the signaling pathway includes cAMP. The phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (200 μM) also mimicked the effect of 5HT on Na+ current, suggesting tonic adenylyl cyclase activity. 5HT reduced the amount of current required to evoke action potentials in type 2 DRG cells, suggesting that 5HT may lower the threshold for activation of nociceptor peripheral receptors. The above data suggest that serotonergic modulation of TTX-resistant Na+channels through a cAMP-dependent signaling pathway in nociceptors may participate in the generation of hyperalgesia.

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