Comparative Analysis of the Mechanisms Underlying Nifedipine-Induced Blockade of Three Subtypes of T-Type Ca<sup>2+</sup>Channels

Shcheglovitov, A. K.; Zhelay, T. I.; Kondratskii, A. P.; Naidenov, V. G.; Shuba, Ya. M.

doi:10.1023/b:neph.0000042560.93321.8c

Cited by 2 publications

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References 29 publications

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“…Earlier, we found that sensitivity to nifedipine of the subunits of LVA calcium channels expressed in Xenopus oocytes is differential [25]. The above blocker much more effectively influenced the current developing due to expression of the α1Н subunit than those determined by expression of other subunits.…”

Section: Resultsmentioning

confidence: 83%

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

et al. 2005

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It was shown earlier that low-threshold calcium current in neurons of the laterodorsal nucleus of the rat thalamus is of a multicomponent nature, and, moreover, its composition changes in the course of postnatal development of the animal. These findings raised a question on the ontogenetic development of expression of the pore-forming subunits of low voltage-activated (LVA) calcium channels (or T-type channels). At present, three isoforms of such subunits, α1G, α1I, and α1H, have been cloned. In our study, we examined expression of mRNA of three subunits of T-type calcium channels in the laterodorsal thalamic nucleus of 1-, 5-, 15-, and 90-day (3-month)-old Wistar rats using reverse transcription and the polymerase chain reaction (PCR). Analysis of amplificates showed that mostly RNAs coding α1G and α1I subunits are expressed in the laterodorsal nucleus of rats of all age groups, while levels of expression RNAs of α1H and α1E subunits (the latter subunit of calcium channels of R type is close in its properties to subunits of LVA channels) are considerably lower (16 or 32 times smaller than the respective values for α1G and α1I subunits). We could not find a significant dependence of the expression of subunit RNAs of the above-mentioned calcium channels on the phases of ontogenetic development. It is possible to hypothesize that the age dynamics of the recorded calcium current in neurons of the laterodorsal thalamic nucleus is not related to increases in the transcription of the corresponding genes but results from post-translational changes in α1G and α1I subunits of proteins of LVA calcium channels or age-related peculiarities of regulation.

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Section: Resultsmentioning

confidence: 83%

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

et al. 2005

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“…Procedures of preparation of matrix RNA (mRNA) of cloned LTCCs and injections of this mRNA into Xenopus oocytes, as well as techniques of isolation and preparation of Xenopus oocytes, were described earlier in detail [15,17].…”

Section: Methodsmentioning

confidence: 99%

Sodium/calcium selectivity of cloned calcium T-type channels

Shcheglovitov

Shuba

2006

Neurophysiology

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We studied the peculiarities of permeability with respect to the main extracellular cations, Na + and Са 2+ , of cloned low-threshold calcium channels (LTCCs) of three subtypes, Ca v 3.1 (α1G), Ca v 3.2 (α1Н), and Ca v 3.3 (α1I), functionally expressed in Xenopus oocytes. In a calcium-free solution containing 100 mM Na + and 5 mM calcium-chelating EGTA buffer (to eliminate residual concentrations of Са 2+ ), we observed considerable integral currents possessing the kinetics of inactivation typical of LTCCs and characterized by reversion potentials of -10 ± 1, -12 ± 1, and -18 ± 2 mV, respectively, for Ca v 3.1, Ca v 3.2, and Ca v 3.3 channels. The presence of Са 2+ in the extracellular solution exerted an ambiguous effect on the examined currents. On the one hand, Са 2+ effectively blocked the current of monovalent cations through cloned LTCCs (K d = 2, 10, and 18 µM for currents through channels Ca v 3.1, Ca v 3.2, and Ca v 3.3, respectively). On the other hand, at the concentration of 1 to 100 mM, Са 2+ itself functioned as a carrier of the inward current. Despite the fact that the calcium current reached the level of saturation in the presence of 5 mM Са 2+ in the external solution, extracellular Na + influenced the permeability of these channels even in the presence of 10 mM Са 2+ . The Ca v 3.3 channels were more permeable with respect to Na + (P Ca /P Na ~ 21) than Ca v 3.1 and Ca v 3.2 (P Ca /P Na ~ 66). As a whole, our data indicate that cloned LTCCs form multi-ion Са 2+ -selective pores, as these ions possess a high affinity for certain binding sites. Monovalent cations present together with Са 2+ in the external solution modulate the calcium permeability of these channels. Among the above-mentioned subtypes, Ca v 3.3 channels show the minimum selectivity with respect to Са 2+ and are most permeable for monovalent cations.

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Comparative Analysis of the Mechanisms Underlying Nifedipine-Induced Blockade of Three Subtypes of T-Type Ca²⁺Channels

Cited by 2 publications

References 29 publications

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

Sodium/calcium selectivity of cloned calcium T-type channels

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Comparative Analysis of the Mechanisms Underlying Nifedipine-Induced Blockade of Three Subtypes of T-Type Ca2+Channels

Cited by 2 publications

References 29 publications

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

Expression of RNA of Subunits of Low-Threshold Calcium Channels in the Laterodorsal Nucleus of the Rat Thalamus: an Ontogenetic Aspect

Sodium/calcium selectivity of cloned calcium T-type channels

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Comparative Analysis of the Mechanisms Underlying Nifedipine-Induced Blockade of Three Subtypes of T-Type Ca²⁺Channels