Dynamic pacing of cell metabolism by intracellular Ca2+ transients.
During cell activation, Ca2+, by stimulating the NADH-producing mitochondrial dehydrogenases, triggers the generation of reducing equivalents whereby ATP production is sustained. In cell populations, [Ca2+] changes in the mitochondrial matrix were demonstrated to parallel rapidly those in the cytosol ([Ca2+]i). There is still no indication as to whether metabolic activation follows oscillatory patterns similar to those of [Ca2+]i. Therefore, changes in NAD(P)H were monitored in single pancreatic beta-cells, adrenal glomerulosa cells, and liver cells during oscillatory [Ca2+]i transients. Rapid NAD(P)H and [Ca2+]i oscillations with similar frequency and sensitive both to changes in glucose concentration and to extracellular Ca2+ removal were identified in a subpopulation of pancreatic beta-cells in primary culture. Furthermore, Ca(2+)-dependent oscillatory NAD(P)H formation could be evoked by the pulsatile application of depolarizing [K+], demonstrating the pacing effect of increased [Ca2+]i on beta-cell metabolism. In adrenal glomerulosa cells, angiotensin II, a physiological stimulator of aldosterone production, could be shown to elicit the oscillatory formation of mitochondrial NAD(P)H through frequency modulation of [Ca2+]i transients. In contrast to the two former endocrine cell types, in hepatocytes, [Arg8]vasopressin and epinephrine caused the amplitude modulation of NAD(P)H formation. Taken together, these results provide unprecedented evidence for a cell-specific pacing of metabolism by [Ca2+]i transients coordinated with cell activation and function.
Department of Medicine, University of Geneva, Centre Médical Universitaire, Switzerland.
W F
WF
Pralong
A
A
Spät
C B
CB
Wollheim
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004734:Energy Metabolism; D004837:Epinephrine / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008564:Membrane Potentials; D009249:NADP / Q000378:metabolism*; D051381:Rats; D015384:Zona Glomerulosa / Q000378:metabolism*
D000804:Angiotensin II; D001127:Arginine Vasopressin; D009249:NADP; D005947:Glucose; D002118:Calcium; D004837:Epinephrine