N-type Ca2+ channels are located on somata, dendrites, and a subpopulation of dendritic spines on live hippocampal pyramidal neurons

1. Intracellular recordings, in conjunction with fura-2 fluorescence imaging, were used to evaluate the contribution of the different Ca2+ channel subtypes to the Ca2+ influx induced by back-propagating trains of action potentials. High-threshold channels contributed mainly to Ca2+ influx in pyramidal cell somata and proximal dendrites, whereas low-threshold and other Ni(2+)-sensitive channels played a greater role in more distal dendritic signaling. These data suggest that the different Ca2+ channel types participate in distinct physiological functions; low-threshold channels likely play a greater role in dendritic integration, whereas high-threshold channels are more important for somatic Ca(2+)-dependent processes.

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Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons

Nature ◽

10.1038/347281a0 ◽

1990 ◽

Vol 347 (6290) ◽

pp. 281-284 ◽

Cited By ~ 329

Author(s):

Ruth E. Westenbroek ◽

Michael K. Ahlijanian ◽

William A. Catterall

Keyword(s):

Pyramidal Neurons ◽

Hippocampal Pyramidal Neurons ◽

Ca2 Channels

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A model for dendritic Ca2+ accumulation in hippocampal pyramidal neurons based on fluorescence imaging measurements

Journal of Neurophysiology ◽

10.1152/jn.1994.71.3.1065 ◽

1994 ◽

Vol 71 (3) ◽

pp. 1065-1077 ◽

Cited By ~ 88

Author(s):

D. B. Jaffe ◽

W. N. Ross ◽

J. E. Lisman ◽

N. Lasser-Ross ◽

H. Miyakawa ◽

...

Keyword(s):

Fluorescence Imaging ◽

Action Potentials ◽

Hippocampal Neurons ◽

Pyramidal Neurons ◽

Na Channels ◽

Hippocampal Pyramidal Neurons ◽

K Channels ◽

Voltage Gated ◽

Synaptic Potentials ◽

Ca2 Channels

1. High-speed fluorescence imaging was used to measure intracellular Ca2+ concentration ([Ca2+]i) changes in hippocampal neurons injected with the Ca(2+)-sensitive indicator fura-2 during intrasomatic and synaptic stimulation. The results of these experiments were used to construct a biophysical model of [Ca2+]i dynamics in hippocampal neurons. 2. A compartmental model of a pyramidal neuron was constructed incorporating published passive membrane properties of these cells, three types of voltage-gated Ca2+ channels characterized from adult hippocampal neurons, voltage-gated Na+ and K+ currents, and mechanisms for Ca2+ buffering and extrusion. 3. In hippocampal pyramidal neurons imaging of Na+ entry during electrical activity suggests that Na+ channels, at least in sufficient density to sustain action potentials, are localized in the soma and the proximal part of the apical dendritic tree. The model, which incorporates this distribution, demonstrates that action potentials attenuate steeply in passive distal dendritic compartments or distal dendritic compartments containing Ca2+ and K+ channels. This attenuation was affected by intracellular resistivity but not membrane resistivity. 4. Consistent with fluorescence imaging experiments, a non-uniform distribution of Ca2+ accumulation was generated by Ca2+ entry through voltage-gated Ca2+ channels opened by decrementally propagating Na+ action potentials. Consequently, the largest increases in [C2+]i were produced in the proximal dendrites. Distal voltage-gated Ca2+ currents were activated by broad, almost isopotential action potentials produced by reducing the overall density of K+ channels. 5. Simulations of subthreshold synaptic stimulation produced dendritic Ca2+ entry by the activation of voltage-gated Ca2+ channels. In the model these Ca2+ signals were localized near the site of synaptic input because of the attenuation of synaptic potentials with distance from the site of origin and the steep voltage-dependence of Ca2+ channel activation. 6. These simulations support the hypotheses generated from experimental evidence regarding the differential distribution of voltage-gated Ca2+ and Na+ channels in hippocampal neurons and the resulting voltage-gated Ca2+ accumulation from action and synaptic potentials.

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Ca2+ Channel Antagonist U-92032 Inhibits Both T-Type Ca2+ Channels and Na+ Channels in Hippocampal CA1 Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.1997.77.2.1023 ◽

1997 ◽

Vol 77 (2) ◽

pp. 1023-1028 ◽

Cited By ~ 14

Author(s):

Robert B. Avery ◽

Daniel Johnston

Keyword(s):

Pyramidal Neurons ◽

Channel Blocker ◽

Cell Voltage ◽

Ionic Currents ◽

Hippocampal Pyramidal Neurons ◽

Voltage Gated ◽

Ca1 Pyramidal Neurons ◽

Hippocampal Ca1 ◽

Old Rats ◽

Ca2 Channels

Avery, Robert B. and Daniel Johnston. Ca2+ channel antagonist U-92032 inhibits both T-type Ca2+ channels and Na+ channels in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 77: 1023–1028, 1997. The effects of 7-[[4-[bis(4-fluoropheny l ) - m e t h y l ] - 1 - p i p e r a z i n y l ] m e t h y l ] - 2 - [ ( 2 - h y d r o x y e t h y l ) a m i n o ]4 -( 1 - m e t h y l e t h y l ) - 2 , 4 , 6 - c y c l o h e p t a t r i e n - 1 - o n e ( U - 9 2 0 3 2 ) , anewly described Ca2+ channel blocker, on voltage-gated ionic currents were measured. Whole cell voltage-clamp records were obtained from acutely isolated CA1 hippocampal pyramidal neurons from 7- to 14-day-old rats. Dimethyl sulfoxide, at either 0.01% or 0.1%, partially inhibited T-type Ca2+ currents (∼20% inhibition) but not high-voltage-activated (HVA) Ca2+ currents. Ethanol (0.2%) did not affect Ca2+ currents. U-92032 selectively inhibited T-type Ca2+ currents (median inhibiting concentration ∼ 500 nM). HVA Ca2+ currents were less sensitive, with ∼75% of the current resistant at 10 μM. Inhibition of Ca2+ currents was reversible. U-92032 inhibited Na+ currents at concentrations similar to those required for T-type currents (>33% block at 1 μM). Block of Na+ currents took several minutes to develop and was irreversible. Voltage-gated K+ currents were insensitive to U-92032 (1 or 10 μM). These results indicate that U-92032 inhibits both T-type Ca2+ channels and Na+ channels, constraining its utility in certain studies. Among Ca2+ channels, however, U-92032 should prove a useful tool for distinguishing physiological contributions of T-type channels.

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Subthreshold synaptic activation of voltage-gated Ca2+ channels mediates a localized Ca2+ influx into the dendrites of hippocampal pyramidal neurons

Journal of Neurophysiology ◽

10.1152/jn.1995.74.3.1335 ◽

1995 ◽

Vol 74 (3) ◽

pp. 1335-1342 ◽

Cited By ~ 135

Author(s):

J. C. Magee ◽

G. Christofi ◽

H. Miyakawa ◽

B. Christie ◽

N. Lasser-Ross ◽

...

Keyword(s):

High Speed ◽

Pyramidal Neurons ◽

Low Voltage ◽

Synaptic Activity ◽

Hippocampal Pyramidal Neurons ◽

Low Concentrations ◽

Hippocampal Ca1 ◽

Apical Dendrites ◽

Whole Cell Recordings ◽

Ca2 Channels

1. Whole cell recordings and high-speed fluorescence imaging were used to investigate the spatial and temporal characteristics of Ca2+ influx during synaptic activity in hippocampal CA1 pyramidal neurons. Brief, subthreshold trains of synaptic potentials elicited by Schaffer collateral stimulation produced transient increases in [Ca2+]i in the apical dendrites near the site of synaptic input. The rises in [Ca2+]i were not due to Ca2+ entry through N-methyl-D-aspartate (NMDA)-activated or non-NMDA-activated glutamate channels, but were reduced by low concentrations of Ni2+. Hyperpolarizing prepulses caused an increase in the synaptically evoked Ca2+ transients, whereas strong hyperpolarization during the train prevented the rise in [Ca2+]i. The data suggest that subthreshold synaptic activity can open low-voltage-activated (T-type) Ca2+ channels and produce a local increase in intradendritic [Ca2+]. Such local increases in [Ca2+]i may be important for modulating the strength of synaptic connections.

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Enhanced Recruitment of Endosomal Na+/H+ Exchanger NHE6 into Dendritic Spines of Hippocampal Pyramidal Neurons during NMDA Receptor-Dependent Long-Term Potentiation

Journal of Neuroscience ◽

10.1523/jneurosci.2583-12.2013 ◽

2013 ◽

Vol 33 (2) ◽

pp. 595-610 ◽

Cited By ~ 27

Author(s):

E. C. Deane ◽

A. E. Ilie ◽

S. Sizdahkhani ◽

M. Das Gupta ◽

J. Orlowski ◽

...

Keyword(s):

Nmda Receptor ◽

Dendritic Spines ◽

Pyramidal Neurons ◽

Long Term Potentiation ◽

Hippocampal Pyramidal Neurons ◽

Term Potentiation

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Ca2+ Channels Involved in the Generation of the Slow Afterhyperpolarization in Cultured Rat Hippocampal Pyramidal Neurons

Journal of Neurophysiology ◽

10.1152/jn.2000.83.5.2554 ◽

2000 ◽

Vol 83 (5) ◽

pp. 2554-2561 ◽

Cited By ~ 61

Author(s):

M. Shah ◽

D. G. Haylett

Keyword(s):

Calcium Channels ◽

Action Potentials ◽

Calcium Release ◽

Pyramidal Neurons ◽

Pyramidal Cells ◽

Isolated Cells ◽

Hippocampal Pyramidal Neurons ◽

Calcium Induced Calcium Release ◽

Ca2 Channels ◽

Hippocampal Pyramidal Cells

The advantages of using isolated cells have led us to develop short-term cultures of hippocampal pyramidal cells, which retain many of the properties of cells in acute preparations and in particular the ability to generate afterhyperpolarizations after a train of action potentials. Using perforated-patch recordings, both medium and slow afterhyperpolarization currents (m I AHP and s I AHP, respectively) could be obtained from pyramidal cells that were cultured for 8–15 days. The s I AHP demonstrated the kinetics and pharmacologic characteristics reported for pyramidal cells in slices. In addition to confirming the insensitivity to 100 nM apamin and 1 mM TEA, we have shown that the s I AHP is also insensitive to 100 nM charybdotoxin but is inhibited by 100 μMd-tubocurarine. Concentrations of nifedipine (10 μM) and nimodipine (3 μM) that maximally inhibit L-type calcium channels reduced the s I AHP by 30 and 50%, respectively. However, higher concentrations of nimodipine (10 μM) abolished the s I AHP, which can be partially explained by an effect on action potentials. Both nifedipine and nimodipine at maximal concentrations were found to reduce the HVA calcium current in freshly dissociated neurons to the same extent. The N-type calcium channel inhibitor, ω-conotoxin GVIA (100 nM), irreversibly inhibited the s I AHP by 37%. Together, ω-conotoxin (100 nM) and nifedipine (10 μM) inhibited the s I AHP by 70%. 10 μM ryanodine also reduced the s I AHP by 30%, suggesting a role for calcium-induced calcium release. It is concluded that activation of the s I AHP in cultured hippocampal pyramidal cells is mediated by a rise in intracellular calcium involving multiple pathways and not just entry via L-type calcium channels.

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Interneurite affinity is regulated by heterophilic nectin interactions in concert with the cadherin machinery

The Journal of Cell Biology ◽

10.1083/jcb.200601089 ◽

2006 ◽

Vol 174 (1) ◽

pp. 141-151 ◽

Cited By ~ 76

Author(s):

Hideru Togashi ◽

Jun Miyoshi ◽

Tomoyuki Honda ◽

Toshiaki Sakisaka ◽

Yoshimi Takai ◽

...

Keyword(s):

Dendritic Spines ◽

Pyramidal Neurons ◽

Hippocampal Pyramidal Neurons ◽

Adhesive Protein ◽

Interneuronal Connections ◽

Immunoglobulin Domain ◽

Genetic Deletion

Neurites recognize their specific partners during the formation of interneuronal connections. In hippocampal pyramidal neurons, axons attach to dendrites for their synaptogenesis, but the dendrites do not form stable contacts with each other, suggesting the presence of a mechanism to allow their selective associations. Nectin-1 (N1), an immunoglobulin domain adhesive protein, is preferentially localized in axons, and its heterophilic partner, N3, is present in both axons and dendrites; we tested their potential roles in interneurite recognition. The overexpression of N1, causing its mislocalization to dendrites, induced atypical dendrodendritic as well as excessive axodendritic associations. On the contrary, the genetic deletion of N1 loosened the contacts between axons and dendritic spines. Those actions of nectins required cadherin–catenin activities, but the overexpression of cadherin itself could not accelerate neurite attachment. These results suggest that the axon-biased localization of N1 and its trans-interaction with N3 in cooperation with the cadherin machinery is critical for the ordered association of axons and dendrites.

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