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Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries.
J Physiol. 2004 May 01; 556(Pt 3):755-71.JP

Abstract

Mitochondria sequester and release calcium (Ca(2+)) and regulate intracellular Ca(2+) concentration ([Ca(2+)](i)) in eukaryotic cells. However, the regulation of different Ca(2+) signalling modalities by mitochondria in smooth muscle cells is poorly understood. Here, we investigated the regulation of Ca(2+) sparks, Ca(2+) waves and global [Ca(2+)](i) by mitochondria in cerebral artery smooth muscle cells. CCCP (a protonophore; 1 microm) and rotenone (an electron transport chain complex I inhibitor; 10 microm) depolarized mitochondria, reduced Ca(2+) spark and wave frequency, and elevated global [Ca(2+)](i) in smooth muscle cells of intact arteries. In voltage-clamped (-40 mV) cells, mitochondrial depolarization elevated global [Ca(2+)](i), reduced Ca(2+) spark amplitude, spatial spread and the effective coupling of sparks to large-conductance Ca(2+)-activated potassium (K(Ca)) channels, and decreased transient K(Ca) current frequency and amplitude. Inhibition of Ca(2+) sparks and transient K(Ca) currents by mitochondrial depolarization could not be explained by a decrease in intracellular ATP or a reduction in sarcoplasmic reticulum Ca(2+) load, and occurred in the presence of diltiazem, a voltage-dependent Ca(2+) channel blocker. Ru360 (10 microm), a mitochondrial Ca(2+) uptake blocker, and lonidamine (100 microm), a permeability transition pore (PTP) opener, inhibited transient K(Ca) currents similarly to mitochondrial depolarization. In contrast, CGP37157 (10 microm), a mitochondrial Na(+)-Ca(2+) exchange blocker, activated these events. The PTP blockers bongkrekic acid and cyclosporin A both reduced inhibition of transient K(Ca) currents by mitochondrial depolarization. These results indicate that mitochondrial depolarization leads to a voltage-independent elevation in global [Ca(2+)](i) and Ca(2+) spark and transient K(Ca) current inhibition. Data also suggest that mitochondrial depolarization inhibits Ca(2+) sparks and transient K(Ca) currents via PTP opening and a decrease in intramitochondrial [Ca(2+)].

Authors+Show Affiliations

Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

14766935

Citation

Cheranov, Serguei Y., and Jonathan H. Jaggar. "Mitochondrial Modulation of Ca2+ Sparks and Transient KCa Currents in Smooth Muscle Cells of Rat Cerebral Arteries." The Journal of Physiology, vol. 556, no. Pt 3, 2004, pp. 755-71.
Cheranov SY, Jaggar JH. Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. J Physiol. 2004;556(Pt 3):755-71.
Cheranov, S. Y., & Jaggar, J. H. (2004). Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. The Journal of Physiology, 556(Pt 3), 755-71.
Cheranov SY, Jaggar JH. Mitochondrial Modulation of Ca2+ Sparks and Transient KCa Currents in Smooth Muscle Cells of Rat Cerebral Arteries. J Physiol. 2004 May 1;556(Pt 3):755-71. PubMed PMID: 14766935.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. AU - Cheranov,Serguei Y, AU - Jaggar,Jonathan H, Y1 - 2004/02/06/ PY - 2004/2/10/pubmed PY - 2005/3/22/medline PY - 2004/2/10/entrez SP - 755 EP - 71 JF - The Journal of physiology JO - J Physiol VL - 556 IS - Pt 3 N2 - Mitochondria sequester and release calcium (Ca(2+)) and regulate intracellular Ca(2+) concentration ([Ca(2+)](i)) in eukaryotic cells. However, the regulation of different Ca(2+) signalling modalities by mitochondria in smooth muscle cells is poorly understood. Here, we investigated the regulation of Ca(2+) sparks, Ca(2+) waves and global [Ca(2+)](i) by mitochondria in cerebral artery smooth muscle cells. CCCP (a protonophore; 1 microm) and rotenone (an electron transport chain complex I inhibitor; 10 microm) depolarized mitochondria, reduced Ca(2+) spark and wave frequency, and elevated global [Ca(2+)](i) in smooth muscle cells of intact arteries. In voltage-clamped (-40 mV) cells, mitochondrial depolarization elevated global [Ca(2+)](i), reduced Ca(2+) spark amplitude, spatial spread and the effective coupling of sparks to large-conductance Ca(2+)-activated potassium (K(Ca)) channels, and decreased transient K(Ca) current frequency and amplitude. Inhibition of Ca(2+) sparks and transient K(Ca) currents by mitochondrial depolarization could not be explained by a decrease in intracellular ATP or a reduction in sarcoplasmic reticulum Ca(2+) load, and occurred in the presence of diltiazem, a voltage-dependent Ca(2+) channel blocker. Ru360 (10 microm), a mitochondrial Ca(2+) uptake blocker, and lonidamine (100 microm), a permeability transition pore (PTP) opener, inhibited transient K(Ca) currents similarly to mitochondrial depolarization. In contrast, CGP37157 (10 microm), a mitochondrial Na(+)-Ca(2+) exchange blocker, activated these events. The PTP blockers bongkrekic acid and cyclosporin A both reduced inhibition of transient K(Ca) currents by mitochondrial depolarization. These results indicate that mitochondrial depolarization leads to a voltage-independent elevation in global [Ca(2+)](i) and Ca(2+) spark and transient K(Ca) current inhibition. Data also suggest that mitochondrial depolarization inhibits Ca(2+) sparks and transient K(Ca) currents via PTP opening and a decrease in intramitochondrial [Ca(2+)]. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/14766935/Mitochondrial_modulation_of_Ca2+_sparks_and_transient_KCa_currents_in_smooth_muscle_cells_of_rat_cerebral_arteries_ L2 - https://doi.org/10.1113/jphysiol.2003.059568 DB - PRIME DP - Unbound Medicine ER -