| 19889626 |
Olson ML, Chalmers S, McCarron JG: Mitochondrial Ca2+ uptake increases Ca2+ release from inositol 1,4,5-trisphosphate receptor clusters in smooth muscle cells. PLoS One. 2009 May 27;4(5):e5701.
Smooth muscle activities are regulated by inositol 1,4,5-trisphosphate (InsP (3))-mediated increases in cytosolic Ca2+ concentration ([Ca2+](c)). Local Ca2+ release from an InsP (3) receptor (InsP (3) R) cluster present on the sarcoplasmic reticulum is termed a Ca2+ puff. Ca2+ released via InsP (3) R 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 InsP (3)-mediated Ca2+ release by preventing a negative feedback effect of high [Ca2+] on InsP (3) R. Mitochondria may regulate InsP (3)-mediated Ca2+ signals by operating between or within InsP (3) R 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 InsP (3)-mediated Ca2+ release by operating within (local) or between (global) InsP (3) R clusters has been addressed. Ca2+ puffs evoked by localized photolysis of InsP (3) in single voltage-clamped colonic smooth muscle cells had amplitudes of 0.5-4.0 F/F (0), durations of approximately 112 ms at half-maximum amplitude, and were abolished by the InsP (3) R inhibitor 2-aminoethoxydiphenyl borate. The protonophore carbonyl cyanide 3-chloropheylhydrazone and complex I inhibitor rotenone each depolarized DeltaPsi (M) to prevent mitochondrial Ca2+ uptake and attenuated Ca2+ puffs by approximately 66 or approximately 60%, respectively. The mitochondrial uniporter inhibitor, RU360, attenuated Ca2+ puffs by approximately 62%. The "fast" Ca2+ chelator 1,2-bis (o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid acted like mitochondria to prolong InsP (3)-mediated Ca2+ release suggesting that mitochondrial influence is via their Ca2+ uptake facility. These results indicate Ca2+ uptake occurs quickly enough to influence InsP (3) R communication at the intra-cluster level and that mitochondria regulate both local and global InsP (3)-mediated Ca2+ signals. |
31(0,1,1,1) |