Divalent cation selectivity of the subtypes of low voltage-activated Ca2+ channels in thalamic neurons

Zhuravleva, Stanislava; Kostyuk, P. G.; Shuba, Yaroslav

doi:10.1097/00001756-199902250-00038

Cited by 12 publications

(15 citation statements)

References 12 publications

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“…According to the expression profile of ␣ 1I and ␣ 1G mRNA in rat brain (23), it was suggested that ␣ 1I and ␣ 1G currents could coexist in thalamic structures. Indeed, it was reported that the LVA current in rat thalamic reticular and laterodorsal neurons could be separated into fast and slow components (16,24,25). By contrast, our Northern and dot blot data have not confirmed that human thalamic structures expressed the ␣ 1I mRNA at high level.…”

Section: Characterization Of Human ␣ 1i T-type Ca 2ϩ Channelscontrasting

confidence: 85%

Specific Properties of T-type Calcium Channels Generated by the Human α1I Subunit

Monteil¹,

Chemin²,

Leuranguer³

et al. 2000

Journal of Biological Chemistry

129

116

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We have cloned and expressed a human ␣ 1I subunit that encodes a subtype of T-type calcium channels. The predicted protein is 95% homologous to its rat counterpart but has a distinct COOH-terminal region. Its mRNA is detected almost exclusively in the human brain, as well as in adrenal and thyroid glands. Calcium currents generated by the functional expression of human ␣ 1I and ␣ 1G subunits in HEK-293 cells were compared. The ␣ 1I current activated and inactivated ϳ10 mV more positively. Activation and inactivation kinetics were up to six times slower, while deactivation kinetics was faster and showed little voltage dependence. A slower recovery from inactivation, a lower sensitivity to Ni 2؉ ions (IC 50 ϳ180 M), and a larger channel conductance (ϳ11 picosiemens) were the other discriminative features of the ␣ 1I current. These data demonstrate that the ␣ 1I subunit encodes T-type Ca 2؉ channels functionally distinct from those generated by the human ␣ 1G or ␣ 1H subunits and point out that human and rat ␣ 1I subunits have species-specific properties not only in their primary sequence, but also in their expression profile and electrophysiological behavior.Voltage-dependent calcium channels control the rapid entry of Ca 2ϩ ions into a wide variety of cell types and are therefore involved in both electrical and cellular signaling. Electrophysiological studies have identified two major Ca 2ϩ channel types as high voltage-activated and low voltage-activated channels (1, 2) with this latter class being also identified as T-type Ca 2ϩ channels (3). T-type Ca 2ϩ channels were originally defined by their activation at low membrane potential, their fast time course, and their small single channel conductance (4, 5). These channels have been identified on a large variety of neurons, and it has become obvious that significant functional diversity exists in the gating behavior of T-type channels, particularly in inactivation kinetics, voltage dependence of steady-state inactivation, and pharmacology (6). The recent identification of several novel genes encoding a subset of homologous Ca 2ϩ channel ␣ 1 subunits, e.g. the ␣ 1G subunit (7-9), the ␣ 1H subunit (10,11), and the rat ␣ 1I subunit (12), has revealed that diversity of T-type voltage-dependent calcium channels is primarily related to the expression of distinct ␣ 1 subunits. Indeed, the expression of the various ␣ 1G and ␣ 1H subunits (7-12) produces Ca 2ϩ currents with the typical signature of T-type channels but with specific features, such as the block by Ni 2ϩ , which discriminates between ␣ 1G and ␣ 1H currents (13). By contrast, the biophysical properties of T-type channels generated by the ␣ 1I subunit markedly differ from those made of ␣ 1G and ␣ 1H subunits (12,14,15), and it was postulated that the ␣ 1I subunit is responsible for native "slow" T-type currents observed in rat thalamic neurons (16). To date the ␣ 1I subunit has only been cloned from rat (12) and whether the ␣ 1I subunit encodes an atypical T-type Ca 2ϩ channel certainly needs further investig...

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Section: Characterization Of Human ␣ 1i T-type Ca 2ϩ Channelscontrasting

confidence: 85%

Specific Properties of T-type Calcium Channels Generated by the Human α1I Subunit

Monteil¹,

Chemin²,

Leuranguer³

et al. 2000

Journal of Biological Chemistry

129

116

View full text Add to dashboard Cite

show abstract

“…None of these agents were absolutely specific for either channel subtype, although nifedipine, flunarizine and La 3 had a distinct preference for the fast channel while the slow one was more sensitive to Ni 2+ . This pharmacology of the fast channel, together with its typical T-type selectivity [20] and large whole-cell current, suggests that this subtype is a representative of the major population of LVA Ca 2+ channels in the central nervous system. Although apparently Ni 2+ sensitive, the slow channel's quite unusual selectivity [20] does not permit its classification simply as the peripheral type.…”

Section: Amplitudes and Densities Of Lva Ca 2+ Currentsmentioning

confidence: 92%

“…In our previous study [20] we used the exponential stripping procedure illustrated in Fig. 1A, B to dissect the overall LVA current into fast and slow components corresponding to the activation of the two subtypes of LVA channels.…”

Section: Kinetic Dissection Of the Currentsmentioning

confidence: 99%

“…In the experiments designed to allow construction of the steady-state activation and inactivation curves, Ba 2+ was used as the charge carrier since it provides a higher proportion of the slow current component [20]. The data for steady-state activation were obtained from the I/V curves of the fast and slow current components by estimating the current change due to the decrease in the driving force by fitting the linear portion of the ascending branch of the I/V with a linear function and dividing, at each potential, the value from the I/V curve by the corresponding value from the line.…”

Section: Steady-state Activation and Inactivationmentioning

confidence: 99%

“…Our own functional studies on thalamocortical neurons of the laterodorsal (LD) thalamic nucleus of the rat suggest that these neurons express two functional subtypes of LVA Ca 2+ channels that, because of their different kinetics of inactivation, have been termed tentatively "fast" and "slow". These channel subtypes differ not only in their voltage dependence, kinetics, pharmacology and selectivity but also in the patterns of their ontogenic expression [17,20]. Given the importance of LVA Ca 2+ channels in determining both normal and pathological firing behaviour of thalamic neurons, the presence of the two subtypes in the same cell raises a number of crucial questions about their physiological roles, distribution on the neuronal surface, pharmacology and relation to the cloned α1 subunits.…”

Section: Introductionmentioning

confidence: 99%

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Subtypes of low voltage-activated Ca 2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles

Zhuravleva

Kostyuk

Shuba

2001

Pfl�gers Archiv European Journal of Physiology

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The macroscopic, low-voltage-activated (LVA or T-type) Ca2+ current in isolated associative (or local-circuit) neurons from the laterodorsal thalamic nucleus of 14-17-day old rats was dissected into two components ("fast" and "slow"), corresponding to the activation of two LVA channel subtypes, based on the difference in the kinetics of inactivation and recovery from inactivation. The steady-state activation and inactivation properties of the channel subtypes endowed slow channels with a substantial window current, whereas fast channels had almost no such current. Fast channels were almost 2 times more sensitive to 30 microM nifedipine (78% inhibition), 10 microM flunarizine (92% inhibition) and 1 microM La3+ (87% inhibition), but about 1.8-fold less sensitive to 100 microM Ni2+ (32% inhibition) than slow channels (40%, 52%, 46% and 56% inhibition respectively). Both channels were almost equally sensitive to 100 microM amiloride (58% and 51% inhibition of fast and slow channels respectively). Comparison of the fast and slow LVA Ca2+ current amplitudes and densities between enzymatically isolated and intact (in brain slices) neurons suggest a predominant localization of the fast channels in soma and the proximal dendrites that remain intact during isolation procedure, whereas the slow channels are more evenly distributed with some preference to the distal areas. These data, together with our previous studies, support the notion of two LVA Ca2+ channel subtypes in associative thalamic neurons and suggest a role for the slow channels in providing the constant Ca2+ influx necessary for the outgrowth of the neurites and for the fast channels in the generation of low-threshold Ca2+ spikes and bursting activity.

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Recent Advances in the Molecular Understanding of Voltage-Gated Ca2+ Channels

Randall

Benham

1999

Molecular and Cellular Neuroscience

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Divalent cation selectivity of the subtypes of low voltage-activated Ca2+ channels in thalamic neurons

Cited by 12 publications

References 12 publications

Specific Properties of T-type Calcium Channels Generated by the Human α1I Subunit

Specific Properties of T-type Calcium Channels Generated by the Human α1I Subunit

Subtypes of low voltage-activated Ca 2+ channels in laterodorsal thalamic neurons: possible localization and physiological roles

Recent Advances in the Molecular Understanding of Voltage-Gated Ca2+ Channels

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