Mitochondrial Ca2+ uptake increases Ca2+ release from Inositol 1,4,5-trisphosphate receptor clusters in smooth muscle cells

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Abstract

Smooth muscle activities are regulated by inositol 1,4,5-trisphosphate (InsP3)-mediated increases in cytosolic Ca2+ concentration ([Ca2+]c). Local Ca2+ release from an InsP3 receptor (InsP3R) cluster present on the sarcoplasmic reticulum is termed a Ca2+ puff. Ca2+ released via InsP3R may diffuse to adjacent clusters to trigger further release and generate a cell-wide (global) Ca2+ rise. In smooth muscle, mitochondrial Ca2+ uptake maintains global InsP3-mediated Ca2+ release by preventing a negative feedback effect of high [Ca2+] on InsP3R. Mitochondria may regulate InsP3-mediated Ca2+ signals by operating between or within InsP3R clusters. In the former mitochondria could regulate only global Ca2+ signals, whereas in the latter both local and global signals would be affected. Here whether mitochondria maintain InsP3-mediated Ca2+ release by operating within (local) or between (global) InsP3R clusters has been addressed. Ca2+ puffs evoked by localized photolysis of InsP3 in single voltage-clamped colonic smooth muscle cells had amplitudes of 0.5-4.0 F/F0, durations of ∼112 ms at half-maximum amplitude, and were abolished by the InsP3R inhibitor 2-aminoethoxydiphenyl borate. The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized ΔΨM to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by ∼66 or ∼60%, respectively. The mitochondrial uniporter inhibitor, RU360, attenuated Ca2+ puffs by ∼62%. The 'fast' Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acted like mitochondria to prolong InsP3-mediated Ca2+ release suggesting that mitochondrial influence is via their Ca2+ uptake facility. These results indicate Ca2+ uptake occurs quickly enough to influence InsP3R communication at the intra-cluster level and that mitochondria regulate both local and global InsP3-mediated Ca2+ signals.
LanguageEnglish
Pages2040-2050
Number of pages11
JournalJournal of Biological Chemistry
Volume285
Issue number3
DOIs
Publication statusPublished - 15 Jan 2010

Fingerprint

Inositol 1,4,5-Trisphosphate Receptors
Mitochondria
Smooth Muscle Myocytes
Muscle
Cells
Smooth Muscle
Rotenone
Inositol 1,4,5-Trisphosphate
Photolysis
Sarcoplasmic Reticulum
Chelating Agents
Feedback
Communication
Electric potential

Keywords

  • smooth muscle
  • Ca2+ uptake
  • Ca2+ release
  • mitochondria
  • inositol 1
  • 4
  • 5-trisphosphate

Cite this

@article{a15962fe08ca4311a3dfc2a91d4824b4,
title = "Mitochondrial Ca2+ uptake increases Ca2+ release from Inositol 1,4,5-trisphosphate receptor clusters in smooth muscle cells",
abstract = "Smooth muscle activities are regulated by inositol 1,4,5-trisphosphate (InsP3)-mediated increases in cytosolic Ca2+ concentration ([Ca2+]c). Local Ca2+ release from an InsP3 receptor (InsP3R) cluster present on the sarcoplasmic reticulum is termed a Ca2+ puff. Ca2+ released via InsP3R may diffuse to adjacent clusters to trigger further release and generate a cell-wide (global) Ca2+ rise. In smooth muscle, mitochondrial Ca2+ uptake maintains global InsP3-mediated Ca2+ release by preventing a negative feedback effect of high [Ca2+] on InsP3R. Mitochondria may regulate InsP3-mediated Ca2+ signals by operating between or within InsP3R clusters. In the former mitochondria could regulate only global Ca2+ signals, whereas in the latter both local and global signals would be affected. Here whether mitochondria maintain InsP3-mediated Ca2+ release by operating within (local) or between (global) InsP3R clusters has been addressed. Ca2+ puffs evoked by localized photolysis of InsP3 in single voltage-clamped colonic smooth muscle cells had amplitudes of 0.5-4.0 F/F0, durations of ∼112 ms at half-maximum amplitude, and were abolished by the InsP3R inhibitor 2-aminoethoxydiphenyl borate. The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized ΔΨM to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by ∼66 or ∼60{\%}, respectively. The mitochondrial uniporter inhibitor, RU360, attenuated Ca2+ puffs by ∼62{\%}. The 'fast' Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acted like mitochondria to prolong InsP3-mediated Ca2+ release suggesting that mitochondrial influence is via their Ca2+ uptake facility. These results indicate Ca2+ uptake occurs quickly enough to influence InsP3R communication at the intra-cluster level and that mitochondria regulate both local and global InsP3-mediated Ca2+ signals.",
keywords = "smooth muscle, Ca2+ uptake, Ca2+ release, mitochondria, inositol 1, 4, 5-trisphosphate",
author = "M. Olson and S. Chalmers and McCarron, {John G.}",
year = "2010",
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volume = "285",
pages = "2040--2050",
journal = "Journal of Biological Chemistry",
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TY - JOUR

T1 - Mitochondrial Ca2+ uptake increases Ca2+ release from Inositol 1,4,5-trisphosphate receptor clusters in smooth muscle cells

AU - Olson, M.

AU - Chalmers, S.

AU - McCarron, John G.

PY - 2010/1/15

Y1 - 2010/1/15

N2 - Smooth muscle activities are regulated by inositol 1,4,5-trisphosphate (InsP3)-mediated increases in cytosolic Ca2+ concentration ([Ca2+]c). Local Ca2+ release from an InsP3 receptor (InsP3R) cluster present on the sarcoplasmic reticulum is termed a Ca2+ puff. Ca2+ released via InsP3R may diffuse to adjacent clusters to trigger further release and generate a cell-wide (global) Ca2+ rise. In smooth muscle, mitochondrial Ca2+ uptake maintains global InsP3-mediated Ca2+ release by preventing a negative feedback effect of high [Ca2+] on InsP3R. Mitochondria may regulate InsP3-mediated Ca2+ signals by operating between or within InsP3R clusters. In the former mitochondria could regulate only global Ca2+ signals, whereas in the latter both local and global signals would be affected. Here whether mitochondria maintain InsP3-mediated Ca2+ release by operating within (local) or between (global) InsP3R clusters has been addressed. Ca2+ puffs evoked by localized photolysis of InsP3 in single voltage-clamped colonic smooth muscle cells had amplitudes of 0.5-4.0 F/F0, durations of ∼112 ms at half-maximum amplitude, and were abolished by the InsP3R inhibitor 2-aminoethoxydiphenyl borate. The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized ΔΨM to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by ∼66 or ∼60%, respectively. The mitochondrial uniporter inhibitor, RU360, attenuated Ca2+ puffs by ∼62%. The 'fast' Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acted like mitochondria to prolong InsP3-mediated Ca2+ release suggesting that mitochondrial influence is via their Ca2+ uptake facility. These results indicate Ca2+ uptake occurs quickly enough to influence InsP3R communication at the intra-cluster level and that mitochondria regulate both local and global InsP3-mediated Ca2+ signals.

AB - Smooth muscle activities are regulated by inositol 1,4,5-trisphosphate (InsP3)-mediated increases in cytosolic Ca2+ concentration ([Ca2+]c). Local Ca2+ release from an InsP3 receptor (InsP3R) cluster present on the sarcoplasmic reticulum is termed a Ca2+ puff. Ca2+ released via InsP3R may diffuse to adjacent clusters to trigger further release and generate a cell-wide (global) Ca2+ rise. In smooth muscle, mitochondrial Ca2+ uptake maintains global InsP3-mediated Ca2+ release by preventing a negative feedback effect of high [Ca2+] on InsP3R. Mitochondria may regulate InsP3-mediated Ca2+ signals by operating between or within InsP3R clusters. In the former mitochondria could regulate only global Ca2+ signals, whereas in the latter both local and global signals would be affected. Here whether mitochondria maintain InsP3-mediated Ca2+ release by operating within (local) or between (global) InsP3R clusters has been addressed. Ca2+ puffs evoked by localized photolysis of InsP3 in single voltage-clamped colonic smooth muscle cells had amplitudes of 0.5-4.0 F/F0, durations of ∼112 ms at half-maximum amplitude, and were abolished by the InsP3R inhibitor 2-aminoethoxydiphenyl borate. The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized ΔΨM to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by ∼66 or ∼60%, respectively. The mitochondrial uniporter inhibitor, RU360, attenuated Ca2+ puffs by ∼62%. The 'fast' Ca2+ chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acted like mitochondria to prolong InsP3-mediated Ca2+ release suggesting that mitochondrial influence is via their Ca2+ uptake facility. These results indicate Ca2+ uptake occurs quickly enough to influence InsP3R communication at the intra-cluster level and that mitochondria regulate both local and global InsP3-mediated Ca2+ signals.

KW - smooth muscle

KW - Ca2+ uptake

KW - Ca2+ release

KW - mitochondria

KW - inositol 1

KW - 4

KW - 5-trisphosphate

U2 - 10.1074/jbc.M109.027094

DO - 10.1074/jbc.M109.027094

M3 - Article

VL - 285

SP - 2040

EP - 2050

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 3

ER -