A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel α1c subunit

Tuvia Perets; Yakov Blumenstein; Elena Shistik; Ilana Lotan; Nathan Dascal

doi:10.1016/0014-5793(96)00303-1

A potential site of functional modulation by protein kinase A in the cardiac Ca²⁺ channel α_1c subunit

Tuvia Perets, Yakov Blumenstein, Elena Shistik, Ilana Lotan, Nathan Dascal^*

^*Corresponding author for this work

Physiology Pharmacology

Tel Aviv University

Research output: Contribution to journal › Article › peer-review

72 Scopus citations

Abstract

The well-characterized enhancement of the cardiac Ca²⁺ L-type current by protein kinase A (PKA) is not observed when the corresponding channel is expressed in Xenopus oocytes, possibly because it is fully phosphorylated in the basal state. However, the activity of the expressed channel is reduced by PKA inhibitors. Using this paradigm as an assay to search for PKA sites relevant to channel modulation, we have found that mutation of serine 1928 of the α_1c subunit to alanine abolishes the modulation of the expressed channel by PKA inhibitors. This effect was independent of the presence of the β subunit. Phosphorylation of serine 1928 of α_1c may mediate the modulatory effect of PKA on the cardiac voltage-dependent Ca²⁺ channel.

Original language	English
Pages (from-to)	189-192
Number of pages	4
Journal	FEBS Letters
Volume	384
Issue number	2
DOIs	https://doi.org/10.1016/0014-5793(96)00303-1
State	Published - 15 Apr 1996

Keywords

Calcium channel
Modulation
Mutation
Protein kinase A
Subunit
Xenopus oocyte

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10.1016/0014-5793(96)00303-1

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title = "A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel α1c subunit",

abstract = "The well-characterized enhancement of the cardiac Ca2+ L-type current by protein kinase A (PKA) is not observed when the corresponding channel is expressed in Xenopus oocytes, possibly because it is fully phosphorylated in the basal state. However, the activity of the expressed channel is reduced by PKA inhibitors. Using this paradigm as an assay to search for PKA sites relevant to channel modulation, we have found that mutation of serine 1928 of the α1c subunit to alanine abolishes the modulation of the expressed channel by PKA inhibitors. This effect was independent of the presence of the β subunit. Phosphorylation of serine 1928 of α1c may mediate the modulatory effect of PKA on the cardiac voltage-dependent Ca2+ channel.",

keywords = "Calcium channel, Modulation, Mutation, Protein kinase A, Subunit, Xenopus oocyte",

author = "Tuvia Perets and Yakov Blumenstein and Elena Shistik and Ilana Lotan and Nathan Dascal",

note = "Funding Information: Acknowledgements: We thank Prof. Veit Flockerzi and Prof. Franz Hofmann for providing the cDNAs of the WT Ca 2+ channel subunits. This work was supported by grants from the Muscular Dystrophy Association and the Israel Academy of Sciences and Humanities.",

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doi = "10.1016/0014-5793(96)00303-1",

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T1 - A potential site of functional modulation by protein kinase A in the cardiac Ca2+ channel α1c subunit

AU - Perets, Tuvia

AU - Blumenstein, Yakov

AU - Shistik, Elena

AU - Lotan, Ilana

AU - Dascal, Nathan

N1 - Funding Information: Acknowledgements: We thank Prof. Veit Flockerzi and Prof. Franz Hofmann for providing the cDNAs of the WT Ca 2+ channel subunits. This work was supported by grants from the Muscular Dystrophy Association and the Israel Academy of Sciences and Humanities.

PY - 1996/4/15

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N2 - The well-characterized enhancement of the cardiac Ca2+ L-type current by protein kinase A (PKA) is not observed when the corresponding channel is expressed in Xenopus oocytes, possibly because it is fully phosphorylated in the basal state. However, the activity of the expressed channel is reduced by PKA inhibitors. Using this paradigm as an assay to search for PKA sites relevant to channel modulation, we have found that mutation of serine 1928 of the α1c subunit to alanine abolishes the modulation of the expressed channel by PKA inhibitors. This effect was independent of the presence of the β subunit. Phosphorylation of serine 1928 of α1c may mediate the modulatory effect of PKA on the cardiac voltage-dependent Ca2+ channel.

AB - The well-characterized enhancement of the cardiac Ca2+ L-type current by protein kinase A (PKA) is not observed when the corresponding channel is expressed in Xenopus oocytes, possibly because it is fully phosphorylated in the basal state. However, the activity of the expressed channel is reduced by PKA inhibitors. Using this paradigm as an assay to search for PKA sites relevant to channel modulation, we have found that mutation of serine 1928 of the α1c subunit to alanine abolishes the modulation of the expressed channel by PKA inhibitors. This effect was independent of the presence of the β subunit. Phosphorylation of serine 1928 of α1c may mediate the modulatory effect of PKA on the cardiac voltage-dependent Ca2+ channel.

KW - Calcium channel

KW - Modulation

KW - Mutation

KW - Protein kinase A

KW - Subunit

KW - Xenopus oocyte

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A potential site of functional modulation by protein kinase A in the cardiac Ca²⁺ channel α_1c subunit

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Keywords

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