Ion channel regulation by calmodulin binding

Saimi, Yoshiro; Kung, Ching

doi:10.1016/0014-5793(94)00782-9

Cited by 71 publications

(50 citation statements)

References 18 publications

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“…The model thus positions CaM's N and C lobe Ca 2ϩ -binding sites within distinct microdomains of the channel. This is of interest in light of the distinct roles played by CaM's N and C lobes in regulating other ion channels (21,22). The location of the RyR1 3614 -3643 target helix within the domain structure of the channel is not defined in existing structural models.…”

Section: Discussionmentioning

confidence: 99%

FRET-based mapping of calmodulin bound to the RyR1 Ca ²⁺ release channel

Cornea

Nitu

Gruber

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

FRET-based mapping of calmodulin bound to the RyR1 Ca ²⁺ release channel

Cornea

Nitu

Gruber

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…It is able to assume myriad conformations specified both by distinct target interaction sites and its own state(s) of bound calcium (Saimi and Kung, 1994;Levitan, 1999;Bhattacharya et al, 2004;Yamniuk and Vogel, 2004). These structural features allow CaM to regulate the function of diverse ion channels: from the best known example of .…”

Section: Discussionmentioning

confidence: 99%

Facilitation of P2X7 Receptor Currents and Membrane Blebbing via Constitutive and Dynamic Calmodulin Binding

Roger¹,

Pelegrı́n²,

Surprenant³

2008

Journal of Neuroscience

112

110

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The ATP-gated P2X 7 receptor (P2X 7 R) is a highly unusual calcium-permeable cationic channel in that within seconds of its activation, dramatic and reversible cytoskeletal rearrangements with prominent membrane blebbing occurs. Agonist-induced membrane currents at hyperpolarized potentials show pronounced facilitation during the initial 30 -100 s of receptor activation but mechanisms responsible have not been elucidated. We measured facilitation of ATP-gated currents in HEK cells expressing rat P2X 7 R and delineated distinct calcium-dependent and independent processes. The calcium-dependent facilitation was composed of an instantaneous (millisecond time domain) and slowly developing (time constant, 20 s with maximum agonist stimulation) component. Both components were prevented when recording with a highly specific calmodulin (CaM) inhibitory peptide but only the instantaneous component was reduced by expression of the dominant-negative EF-handless CaM mutant. Coimmunoprecipitation assays detected low levels of CaM binding to unstimulated P2X 7 R, and this increased by 50% during 45 s stimulation of the receptor. We identified a novel 1-5-16 Ca 2ϩ -dependent CaM binding motif in the intracellular C terminus of P2X 7 R; mutations in this domain resulted in the absence of calcium-dependent facilitation and binding of CaM to unstimulated or stimulated receptor. Blockade of CaM binding also delayed membrane blebbing by threefold. Our results demonstrate that CaM binds constitutively to closed P2X 7 R channels and dynamically during channel activation to significantly enhance and prolong calcium entry. This is the first example of CaM deregulating, rather than tightly controlling, calcium entry through an ion channel.

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“…Although second messenger cascades involving CAM are known to modulate many ion channels (48), there is growing evidence of regulation by Ca 2ϩ -CAM through direct binding (49). These phenomena have been documented for the Paramecium Ca 2ϩ -activated sodium channels (50), the Drosophila Ca 2ϩ -permeable channels trp and trpl (51,52), the vertebrate photoreceptors and olfactory receptors involving cyclic nucleotide gated channels (53), the ryanodine receptor Ca 2ϩ -release channels (54), and the N-methyl-D-aspartate receptors (55).…”

Section: Discussionmentioning

confidence: 99%