ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites

Ilya Bezprozvanny; Barbara E. Ehrlich

doi:10.1016/0896-6273(93)90065-Y

ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites

Ilya Bezprozvanny, Barbara E. Ehrlich

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151 Scopus citations

Abstract

The inositol 1,4,5-trisphosphate (IP₃) receptor, a Ca²⁺permeable channel, plays a key role in intracellular Ca²⁺ signaling. The effects of ATP on the IP₃ receptor at the single-channel level were characterized after channel incorporation into planar lipid bilayers. ATP alone was not sufficient to open the IP₃-gated channel, but addition of ATP or nonhydrolyzable ATP analogs in the presence of IP₃ increased the frequency of channel openings 4.8-fold and increased the average duration of channel openings 2.5-fold; channel conductance was unchanged. High concentrations of ATP (>4 mM) decreased channel activity most probably by competing with IP₃ for the IP₃-binding site. Allosteric modulation of IP₃-induced Ca²⁺ release by ATP may contribute to the maintenance of cell viability during periods of energy starvation.

Original language	English (US)
Pages (from-to)	1175-1184
Number of pages	10
Journal	Neuron
Volume	10
Issue number	6
DOIs	https://doi.org/10.1016/0896-6273(93)90065-Y
State	Published - Jun 1993

ASJC Scopus subject areas

General Neuroscience

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@article{ca25334396514856bd44539c016b1fc3,

title = "ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites",

abstract = "The inositol 1,4,5-trisphosphate (IP3) receptor, a Ca2+permeable channel, plays a key role in intracellular Ca2+ signaling. The effects of ATP on the IP3 receptor at the single-channel level were characterized after channel incorporation into planar lipid bilayers. ATP alone was not sufficient to open the IP3-gated channel, but addition of ATP or nonhydrolyzable ATP analogs in the presence of IP3 increased the frequency of channel openings 4.8-fold and increased the average duration of channel openings 2.5-fold; channel conductance was unchanged. High concentrations of ATP (>4 mM) decreased channel activity most probably by competing with IP3 for the IP3-binding site. Allosteric modulation of IP3-induced Ca2+ release by ATP may contribute to the maintenance of cell viability during periods of energy starvation.",

author = "Ilya Bezprozvanny and Ehrlich, {Barbara E.}",

note = "Funding Information: We thank J. Watras, A. Finkelstein, A. P. Naumov, and C. N. Mozhaeva for helpful discussions, S. Bezprozvannaya for expert technical assistance, and P. Ascher, L. B. Cohen, I. Levitan, and A. M. Katz for comments on the manuscript. 1. B. was a Grass Fellow in Neurophysiology and H. B. Steinbach Fellow of the MBL. This work was supported by National Institutes of Health grants HL 33026 and GM 39029.",

year = "1993",

month = jun,

doi = "10.1016/0896-6273(93)90065-Y",

language = "English (US)",

volume = "10",

pages = "1175--1184",

journal = "Neuron",

issn = "0896-6273",

publisher = "Cell Press",

number = "6",

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T1 - ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites

AU - Bezprozvanny, Ilya

AU - Ehrlich, Barbara E.

N1 - Funding Information: We thank J. Watras, A. Finkelstein, A. P. Naumov, and C. N. Mozhaeva for helpful discussions, S. Bezprozvannaya for expert technical assistance, and P. Ascher, L. B. Cohen, I. Levitan, and A. M. Katz for comments on the manuscript. 1. B. was a Grass Fellow in Neurophysiology and H. B. Steinbach Fellow of the MBL. This work was supported by National Institutes of Health grants HL 33026 and GM 39029.

PY - 1993/6

Y1 - 1993/6

N2 - The inositol 1,4,5-trisphosphate (IP3) receptor, a Ca2+permeable channel, plays a key role in intracellular Ca2+ signaling. The effects of ATP on the IP3 receptor at the single-channel level were characterized after channel incorporation into planar lipid bilayers. ATP alone was not sufficient to open the IP3-gated channel, but addition of ATP or nonhydrolyzable ATP analogs in the presence of IP3 increased the frequency of channel openings 4.8-fold and increased the average duration of channel openings 2.5-fold; channel conductance was unchanged. High concentrations of ATP (>4 mM) decreased channel activity most probably by competing with IP3 for the IP3-binding site. Allosteric modulation of IP3-induced Ca2+ release by ATP may contribute to the maintenance of cell viability during periods of energy starvation.

AB - The inositol 1,4,5-trisphosphate (IP3) receptor, a Ca2+permeable channel, plays a key role in intracellular Ca2+ signaling. The effects of ATP on the IP3 receptor at the single-channel level were characterized after channel incorporation into planar lipid bilayers. ATP alone was not sufficient to open the IP3-gated channel, but addition of ATP or nonhydrolyzable ATP analogs in the presence of IP3 increased the frequency of channel openings 4.8-fold and increased the average duration of channel openings 2.5-fold; channel conductance was unchanged. High concentrations of ATP (>4 mM) decreased channel activity most probably by competing with IP3 for the IP3-binding site. Allosteric modulation of IP3-induced Ca2+ release by ATP may contribute to the maintenance of cell viability during periods of energy starvation.

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JO - Neuron

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IS - 6

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ATP modulates the function of inositol 1,4,5-trisphosphate-gated channels at two sites

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