| 14766935 |
Cheranov SY, Jaggar JH: Mitochondrial modulation of Ca2+ sparks and transient KCa currents in smooth muscle cells of rat cerebral arteries. J Invest Dermatol. 1996 Nov;107(5):720-5.
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+)]. |
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