Effects of IP3, Spermine, and Mg2+ on Regulation of Ca2+ Transport by Endoplasmic Reticulum and Mitochondria in Permeabilized Pancreatic Islets

Lenzen, Sigurd; Rustenbeck, Ingo

doi:10.2337/diab.40.3.323

Cited by 23 publications

(10 citation statements)

References 12 publications

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“…IP 3 is known to mobilize Ca 2+ by binding to receptors on the endoplasmic reticulum or a portion thereof (44,45). Intracellular effects of IP 3 have previously been studied in subcellular fractions of rat insulinoma cells (42), in various permeabilized insulin-secreting cell lines (13)(14)(15)(16), permeabilized islets (10,11,46), and islet cells (12,13). In the present study, individual (3-cells were analyzed with regard to the action of IP 3 on Ca 2+ sequestered in the organelles.…”

Section: Fig 6 Effects Of Mitochondrial Inhibition On Organelle Ca mentioning

confidence: 99%

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In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

et al. 1998

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Free Ca2+ was measured in intracellular stores of individual mouse pancreatic beta-cells using dual-wavelength microfluorometry and the low-affinity Ca2+ indicator furaptra. Controlled permeabilization of the plasma membrane with 4 micromol/l digitonin revealed that 22% of the furaptra was trapped in intracellular nonnuclear compartments. When 3 mmol/l ATP and 200 nmol/l Ca2+ were simultaneously present, this cation rapidly accumulated in the organelle pool, reaching an average concentration of 200-500 micromol/l. Whereas agents affecting the mitochondrial function (5 mmol/l succinate, 2 micromol/l ruthenium red, or 10 micromol/l antimycin A + 2 microg/ml oligomycin) had little effects, the Ca2+-ATPase inhibitor thapsigargin released 92% of the Ca2+ mobilizable with the ionophore Br-A23187. Digital imaging revealed regional differences in the organelle Ca2+. The regions with the highest Ca2+ concentration were particularly responsive to inositol 1,4,5-trisphosphate (IP3). IP3 mobilized Ca2+ in a dose-dependent way with half-maximal and maximal effects at about 1 and 5 micromol/l, respectively. High concentrations of IP3 released about half of the thapsigargin-sensitive Ca2+, but there were no responses to agents known to activate ryanodine receptors, such as 10 mmol/l caffeine, 0.1-1 micromol/l ryanodine, or 1-5 micromol/l cyclic ADP ribose. The results reinforce the concept that mobilization of intracellular Ca2+ in the pancreatic beta-cell is mediated by IP3 receptors rather than ryanodine receptors.

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Section: Fig 6 Effects Of Mitochondrial Inhibition On Organelle Ca mentioning

confidence: 99%

“…So far, intracellular Ca 2+ stores have been characterized after permeabilization of islets (10,11), islet cells (12,13), or insulinsecreting cell lines (13)(14)(15)(16) using extracellular fluorescent indicators, microelectrodes, or radiotracer methods. However, these techniques cannot be applied to individual cells.…”

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confidence: 99%

In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

et al. 1998

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“…Taken together these results implicate that SP affects intracellular Ca 2+ release at a step between G‐protein activation and the formation of IP 3 . Spermine has been shown to increase Ca 2+ uptake in heart, liver and brain mitochondria, suggesting that SP affects cytosolic [Ca 2+ ] also via this mechanism (Lenzen & Rustenbeck 1991, Lenzen et al . 1992, Rustenbeck et al .…”

Section: Intracellular Ca2+ Release and Uptakementioning

confidence: 99%

Regulation of Ca²⁺ channel and phosphatase activities by polyamines in intestinal and vascular smooth muscle – implications for cellular growth and contractility

Nilsson

Gomez

Swärd

et al. 2002

Acta Physiologica Scandinavica

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Polyamines added extracellularly to intestinal and vascular smooth muscle cells cause relaxation through inhibition of Ca2+ channel activity. Intracellularly applied polyamines also affect Ca2+ channel properties. Polyamines do not readily pass over the plasma membrane because of their positive charges but in permeabilized smooth muscle preparations they have free access to the cytoplasm. In this system they increase sensitivity of the contractile machinery to Ca2+ through inhibition of myosin phosphatase activity. The magnitude of Ca2+ channel and phosphatase inhibition depends on the number of positive charges on the polyamine molecule. Polyamines have an obligatory, but yet undefined, role in regulation of cell growth and proliferation. Several groups of protein kinases, such as tyrosine and mitogen activated protein (MAP)‐kinases transmit the growth signal from the plasma membrane to the cell nucleus where mitosis and protein synthesis are initiated. The data reviewed here show that polyamines may affect such signal transmission via inhibition of phosphatase activity.

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“…More recently, the effects of spermine on mitochondrial Ca2+ transport have attracted considerable attention. However, although an early study by Akerman (1977) described an inhibition of mitochondrial Ca2+ uptake by spermine, many subsequent studies reported a stimulatory effect of spermine on Ca2+ uptake by mitochondria from liver (Nicchitta & Williamson, 1984;Lenzen et al, 1986;Kroner, 1988;McCormack, 1989), hepatoma cells (Fiskum, 1985), brain (Lenzen et al, 1986;Jensen et al, 1987Jensen et al, , 1989Rottenberg & Marbach, 1990), heart (Lenzen et al, 1986;McCormack, 1989), kidney (McCormack, 1989) and pancreatic islets (Lenzen & Rustenbeck, 1991). Surprisingly, however, for unknown reasons rather different half-maximally effective concentrations were reported (Nicchitta & Williamson, 1984;Lenzen et al, 1986;Jensen et al, 1987;Kroner, 1988;McCormack, 1989).…”

Section: Introductionmentioning

confidence: 99%

Dual effect of spermine on mitochondrial Ca2+ transport

Lenzen

Münster

Rustenbeck

1992

Biochemical Journal

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1. A dual effect of the polyamine spermine on Ca2+ uptake by isolated rat liver, brain and heart mitochondria could be demonstrated by using a high-resolution system for studying mitochondrial Ca2+ transport. Depending on the experimental situation, spermine had an inhibiting or accelerating effects on mitochondrial Ca(2+)-uptake rate, but invariably increased the mitochondrial Ca2+ accumulation. 2. Both effects were concentration-dependent and clearly discernible on the basis of their different kinetic characteristics. For mitochondria from all three tissues the half-maximally effective concentration for inhibition of the initial rate of Ca2+ uptake was approx. 180 microM, whereas that for the subsequent stimulation of Ca2+ accumulation was approx. 50 microM. 3. Acceleration of the initial uptake rate could be seen when the mitochondria were preloaded with spermine during a 2 min preincubation period and thereafter incubated in a medium without spermine. 4. When such spermine-preloaded mitochondria were incubated in a spermine-containing medium, the increase in Ca(2+)-accumulation capacity was maintained in spite of an unchanged rate of Ca2+ uptake. 5. Mg2+ interacted with the effects of spermine in a differential manner, enhancing the initial inhibition of the rate of mitochondrial Ca2+ uptake and diminishing the subsequent stimulation of mitochondrial Ca2+ accumulation. 6. This dual effect of spermine on mitochondrial Ca2+ transport resolves the apparent paradox that a polycationic compound can act as a stimulator of Ca2+ uptake.

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Effects of IP3, Spermine, and Mg2+ on Regulation of Ca2+ Transport by Endoplasmic Reticulum and Mitochondria in Permeabilized Pancreatic Islets

Cited by 23 publications

References 12 publications

In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

Regulation of Ca²⁺ channel and phosphatase activities by polyamines in intestinal and vascular smooth muscle – implications for cellular growth and contractility

Dual effect of spermine on mitochondrial Ca2+ transport

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Effects of IP3, Spermine, and Mg2+ on Regulation of Ca2+ Transport by Endoplasmic Reticulum and Mitochondria in Permeabilized Pancreatic Islets

Cited by 23 publications

References 12 publications

In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

In Situ Characterization of Nonmitochondrial Ca2+ Stores in Individual Pancreatic β-Cells

Regulation of Ca2+ channel and phosphatase activities by polyamines in intestinal and vascular smooth muscle – implications for cellular growth and contractility

Dual effect of spermine on mitochondrial Ca2+ transport

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Regulation of Ca²⁺ channel and phosphatase activities by polyamines in intestinal and vascular smooth muscle – implications for cellular growth and contractility