Repetitive mitochondrial Ca2+ signals synchronize with cytosolic Ca2+ oscillations in the pancreatic beta-cell line, MIN6.

We examined the relationship between cytosolic Ca²⁺ concentration ([Ca²⁺]_c) and mitochondrial matrix Ca²⁺ concentration ([Ca²⁺]_m) in the pancreatic beta-cell line, MIN6. [Ca²⁺]_c was monitored in a single or a group (30 cells) of fura-2-loaded MIN6 cells, and [Ca²⁺]_m was measured in a group (1 × 10⁶ cells) of MIN6 cells stably transfected with aequorin targeted at the mitochondria. Exogenous ATP (0.25 mmol/l) produced a single transient increase in [Ca²⁺]_c whereas 22 mmol/l KCl produced a sustained plateau increase. ATP and KCl evoked transient increases in [Ca²⁺]_m but with distinct time courses of [Ca²⁺]_m decline: the [Ca²⁺]_m increase induced by ATP decreased more rapidly than that induced by KCl. Nitrendipine (3 μmol/l), a blocker of L-type Ca²⁺ channels, inhibited both [Ca²⁺]_c and [Ca²⁺]_m signals in response to KCl and tolbutamide, but not those to ATP. Peak levels of [Ca²⁺]_m increase (around 2 μmol/l) exceeded those of [Ca²⁺]_c increase (around 500 nmol/l). A rise in glucose concentration from 3 to 30 mmol/l induced oscillations of [Ca²⁺]_c that overlay the sustained increases in [Ca²⁺]_c in single cells. An oscillatory increase in [Ca²⁺]_m was similarly observed in response to glucose. Addition of 10 mmol/l 2-ketoisocaproic acid at 20 mmol/l glucose further increased the plateau level of [Ca²⁺]_c and the frequency of [Ca²⁺]_c oscillations, which were correlated with a further increase in [Ca²⁺]_m. In response to pulsatile exposure to KCl, [Ca²⁺]_c and [Ca²⁺]_m increased synchronously. These data suggest that an oscillatory increase in [Ca²⁺]_m in beta cells, the signal which is thought to be necessary for continuous stimulation of mitochondrial metabolism, is produced synchronously with the [Ca²⁺]_c oscillations. [Diabetologia (1998) 41: 279–286] [ABSTRACT FROM AUTHOR]