Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

Igor Dzhura; Yuejin Wu; Roger J. Colbran; Jeffrey R. Balser; Mark E. Anderson

doi:10.1038/35004052

Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

Igor Dzhura, Yuejin Wu, Roger J. Colbran, Jeffrey R. Balser, Mark E. Anderson

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

297 Scopus citations

Abstract

A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (I(Ca)) in response to increased intracellular Ca²⁺ concentrations. The Ca²⁺-binding protein calmodulin (CAM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca²⁺/CaM-dependent facilitation are unknown. Here we show that the Ca²⁺/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for I(Ca) facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca²⁺ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca²⁺/CaM-dependent I(Ca) facilitation.

Original language	English (US)
Pages (from-to)	173-177
Number of pages	5
Journal	Nature cell biology
Volume	2
Issue number	3
DOIs	https://doi.org/10.1038/35004052
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

Cell Biology

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title = "Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels",

abstract = "A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (I(Ca)) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CAM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for I(Ca) facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent I(Ca) facilitation.",

author = "Igor Dzhura and Yuejin Wu and Colbran, {Roger J.} and Balser, {Jeffrey R.} and Anderson, {Mark E.}",

note = "Funding Information: ACKNOWLEDGEMENTS This work was supported by grants from the NIH (grants NHLBI, HL03727 and HL62494 to M.E.A.) and the American Heart Association (to M.E.A. and R.J.C.). J.R.B. is an Established Investigator of the American Heart Association. We thank M. Bass for technical assistance, and D. Roden and A. George for helpful criticisms and suggestions. Correspondence and requests for materials should be addressed to M.E.A.",

year = "2000",

doi = "10.1038/35004052",

language = "English (US)",

volume = "2",

pages = "173--177",

journal = "Nature cell biology",

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T1 - Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

AU - Dzhura, Igor

AU - Wu, Yuejin

AU - Colbran, Roger J.

AU - Balser, Jeffrey R.

AU - Anderson, Mark E.

N1 - Funding Information: ACKNOWLEDGEMENTS This work was supported by grants from the NIH (grants NHLBI, HL03727 and HL62494 to M.E.A.) and the American Heart Association (to M.E.A. and R.J.C.). J.R.B. is an Established Investigator of the American Heart Association. We thank M. Bass for technical assistance, and D. Roden and A. George for helpful criticisms and suggestions. Correspondence and requests for materials should be addressed to M.E.A.

PY - 2000

Y1 - 2000

N2 - A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (I(Ca)) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CAM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for I(Ca) facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent I(Ca) facilitation.

AB - A dynamic positive feedback mechanism, known as 'facilitation', augments L-type calcium-ion currents (I(Ca)) in response to increased intracellular Ca2+ concentrations. The Ca2+-binding protein calmodulin (CAM) has been implicated in facilitation, but the single-channel signature and the signalling events underlying Ca2+/CaM-dependent facilitation are unknown. Here we show that the Ca2+/CaM-dependent protein kinase II (CaMK) is necessary and possibly sufficient for I(Ca) facilitation. CaMK induces a channel-gating mode that is characterized by frequent, long openings of L-type Ca2+ channels. We conclude that CaMK-mediated phosphorylation is an essential signalling event in triggering Ca2+/CaM-dependent I(Ca) facilitation.

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JO - Nature cell biology

JF - Nature cell biology

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Calmodulin kinase determines calcium-dependent facilitation of L-type calcium channels

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