N-Type Calcium Channels in the Developing Rat Hippocampus: Subunit, Complex, and Regional Expression

Jones, Owen; Bernstein, Geula M.; Jones, E. G.; Jugloff, Denis G.M.; Law, Marcus; Wong, Wei; Mills, Linda R.

doi:10.1523/jneurosci.17-16-06152.1997

Cited by 59 publications

(38 citation statements)

References 80 publications

(158 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, activation of PKA was shown to antagonize ethanol modulation of N-and P/Q-type VGCCs in PC12 cells (Solem et al, 1997). N-type channel subunit composition modifications during development could be an additional explanation for the different sensitivity to ethanol throughout maturation (Jones et al, 1997;Vance et al, 1998;Lin et al, 1999;Pan and Lipscombe, 2000) Our findings are consistent with several reports indicating that these channels are important targets of ethanol. Through their modulation, ethanol inhibits dopamine release from rat striatal synaptosomes (Woodward et al, 1990), vasopressin release from rat neurohypophysial nerve terminals (Wang et al, 1991), and depolarization-induced rises in [Ca 2ϩ ] i in PC12 cells (Solem et al, 1997).…”

Section: Ethanol Affects Glutamatergic Synaptic Currents In Neonatal supporting

confidence: 92%

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Mameli¹,

Zamudio²,

Carta³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

Ethanol exposure during fetal development is a leading cause of learning disabilities. Studies suggest that it alters learning and memory by permanently damaging the hippocampus. It is generally assumed that this is mediated, in part, via alterations in glutamatergic transmission. Although NMDA receptors are presumed to be the most sensitive targets of ethanol in immature neurons, this issue has not been explored in the developing hippocampus. We performed whole-cell patch-clamp recordings in hippocampal slices from neonatal rats. Unexpectedly, we found that acute ethanol (10 -50 mM) exposure depresses inward currents elicited by local application of exogenous AMPA, but not NMDA, in CA3 pyramidal neurons. These findings revealed a direct effect of ethanol on postsynaptic AMPA receptors. Ethanol significantly decreased the amplitude of both AMPA and NMDA receptor-mediated EPSCs evoked by electrical stimulation. This effect was associated with an increase in the paired-pulse ratio and a decrease in the frequency of miniature EPSCs driven by depolarization of axonal terminals. These findings demonstrate that ethanol also acts at the presynaptic level. -Conotoxin-GVIA occluded the effect of ethanol on NMDA EPSCs, indicating that ethanol decreases glutamate release via inhibition of N-type voltage-gated Ca 2ϩ channels. In more mature rats, ethanol did not affect the probability of glutamate release or postsynaptic AMPA receptor-mediated currents, but it did inhibit NMDA-mediated currents. We conclude that the mechanism by which ethanol inhibits glutamatergic transmission is age dependent and challenge the view that postsynaptic NMDA receptors are the primary targets of ethanol early in development.

show abstract

Section: Ethanol Affects Glutamatergic Synaptic Currents In Neonatal supporting

confidence: 92%

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Mameli¹,

Zamudio²,

Carta³

et al. 2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Previously, correlations in the localization and density of ␣ 1 and ␤ isoform mRNA in adult, embryonic, and postnatal rat brain predicted likely ␣ 1 /␤ complexes (48), but there were no conclusions reached in the case of the ␣ 1B/␤ complex. Another study concluded that there was no evidence for subunit switching in developing hippocampus as they targeted only the ␣ 1B /␤3 heteromultimers for analysis (59). In this study we have identified clear developmental trends in ␣ 1B /␤ composition from a population predominant in ␣ 1B ϩ ␤1b complexes (P2) to a population comprised of ␣ 1B ϩ ␤3 and ␣ 1B ϩ ␤4 complexes in mature rat brain.…”

Section: Figmentioning

confidence: 59%

Differential Expression and Association of Calcium Channel α1B and β Subunits during Rat Brain Ontogeny

Vance

Begg

Lee

et al. 1998

Journal of Biological Chemistry

View full text Add to dashboard Cite

Calcium functions as an essential second messenger during neuronal development and synapse acquisition. Voltage-dependent calcium channels (VDCC), which are critical to these processes, are heteromultimeric complexes composed of ␣ 1 , ␣ 2 /␦, and ␤ subunits. ␤ subunits function to direct the VDCC complex to the plasma membrane as well as regulate its channel properties. The importance of ␤ to neuronal functioning was recently underscored by the identification of a truncated ␤4 isoform in the epileptic mouse lethargic ( These results suggested that subsequent maturation of ␣ 1B or its assembly with auxiliary subunits was required to exhibit high affinity 125 I-CTX binding. The temporal pattern of expression of ␤ subunits and their assembly with ␣ 1B indicated a developmental pattern of expression of ␤ isoforms: ␤1b increased 3-fold from P0 to adult, ␤4 increased 10-fold, and both ␤2 and ␤3 expression remained unchanged. As the ␤ component of N-type VDCC changed during postnatal development, we were able to identify both immature and mature forms of N-type VDCC. At P2, the relative contribution of ␤ is ␤1b > ␤3 > > ␤2, whereas at P14 and adult the distribution is ␤3 > ␤1b ‫؍‬ ␤4. Although we observed no ␤4 associated with the ␣ 1B at P2, ␤4 accounted for 14 and 25% of total ␣ 1B /␤ subunit complexes in P14 and adult, respectively. Thus, of the ␤ isoforms analyzed, only the ␤4 was assembled with the rat ␣ 1B to form N-type VDCC with a time course that paralleled its level of expression during rat brain development. These results suggest a role for the ␤4 isoform in the assembly and maturation of the N-type VDCC.

show abstract

“…Protein samples were prepared, electrophoresed, and transferred to nitrocellulose as described previously (26). The nitrocellulose membranes were incubated overnight at 4°C with the Kv4.2 polyclonal antibody at 1:1000.…”

Section: Methodsmentioning

confidence: 99%

Cell Surface Targeting and Clustering Interactions between Heterologously Expressed PSD-95 and the Shal Voltage-gated Potassium Channel, Kv4.2

Wong¹,

Newell²,

Jugloff³

et al. 2002

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Kv4.2 is a voltage-gated potassium channel that is critical in controlling the excitability of myocytes and neurons. Processes that influence trafficking and surface distribution patterns of Kv4.2 will affect its ability to contribute to cellular functions. The scaffolding/clustering protein PSD-95 regulates trafficking and distribution of several receptors and Shaker family Kv channels. We therefore investigated whether the C-terminal valine-serine-alanine-leucine (VSAL) of Kv4.2 is a novel binding motif for PSD-95. By using co-immunoprecipitation assays, we determined that full-length Kv4.2 and PSD-95 interact when co-expressed in mammalian cell lines. Mutation analysis in this heterologous expression system showed that the VSAL motif of Kv4.2 is necessary for PSD-95 binding. PSD-95 increased the surface expression of Kv4.2 protein and caused it to cluster, as shown by deconvolution microscopy and biotinylation assays. Deleting the C-terminal VSAL motif of Kv4.2 eliminated these effects, as did substituting a palmitoylation-deficient PSD-95 mutant. In addition to these effects of PSD-95 on Kv4.2 distribution, the channel itself promoted redistribution of PSD-95 to the cell surface in the heterologous expression system. This work represents the first evidence that a member of the Shal subfamily of Kv channels can bind to PSD-95, with functional consequences.The influence that voltage-gated ion channels exert on the integrative physiology of excitable cells is determined by the inherent biophysical properties of the channels and their cell surface distribution. Kv4.2 is a fast transient (A-type) voltagegated potassium (Kv) 1 channel of the Shal subfamily that is found in heart and neurons (1). In myocytes, Kv4.2 is a major component of the I to current, which is crucial for recovery from the QT interval and for repolarization (2). In neurons of the central nervous system, Kv4.2 is expressed primarily somatodendritically (3, 4), where its concentration at postsynaptic sites may affect the back propagation of action potentials (5) and may therefore modulate long term potentiation at synapses (6). In contrast, Kv1.4, a Kv channel of the Shaker subfamily, is primarily expressed on axons (3, 4). Its positioning along the axon and at presynaptic sites (7-9) is thought to regulate the efficiency of action potential propagation (10) and to control neurotransmitter release (11). It is therefore crucial to understand the basis for the specialized distributions of Kv channels in order to fully understand their roles in neuronal excitability. The mechanisms that specify ion channel distributions are not well known and likely differ between those that determine localization in sub-domains of cells (e.g. axon, soma, and dendrite) versus lateral organization at the membrane, such as within channel clusters. Post-synaptic density 95 (PSD-95) is a membrane-associated guanylate kinase that helps localize and cluster numerous proteins. Kv1.4 and other Kv1 members are among the best known examples of in vitro ion channel clusteri...

show abstract

N-Type Calcium Channels in the Developing Rat Hippocampus: Subunit, Complex, and Regional Expression

Cited by 59 publications

References 80 publications

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Developmentally Regulated Actions of Alcohol on Hippocampal Glutamatergic Transmission

Differential Expression and Association of Calcium Channel α1B and β Subunits during Rat Brain Ontogeny

Cell Surface Targeting and Clustering Interactions between Heterologously Expressed PSD-95 and the Shal Voltage-gated Potassium Channel, Kv4.2

Contact Info

Product

Resources

About