Pathways for the movements of ions during calcium-free perfusion and the induction of the ‘calcium paradox’

Tunstall, J.; Busselen, P.; Rodrigo, Glenn C.; Chapman, Reg

doi:10.1016/s0022-2828(86)80406-0

Cited by 34 publications

(21 citation statements)

References 60 publications

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“…Although these preparations were quiescent, it has been suggested that a calcium-free perfusate might alter the voltage dependence and channel specificity ofthe sodium and calcium channel (12,22,26). Therefore, we exposed muscles during 15 min ofa calcium-free period to IO-' M ofthe calcium channel blocker, nitrendipine (n = 3), 10-4 M of the sodium channel blocker, tetrodotoxin (n -3), or low doses (10-6 M) of the Na+/Ca2+ and Na+/H', exchange blocker, amiloride 10-6 M (n -4), or the amiloride analogue, dichlorobenzamil (I0-`M) (n -3) ( Table II).…”

Section: Resultsmentioning

confidence: 99%

“…Tunstall et al (12), using sodium electrodes in four preparations, recently demonstrated in frog atria that a NaW rises to 58 mmol/liter over an unspecified period of calcium-free perfusion. Before this, Ruano-Arroyo et al, (7) used isotope techniques to demongrate that cell sodium content was related to cellular calcium, potassium loss, and decreased contractile function during calcium readmission.…”

Section: Discussionmentioning

confidence: 99%

“…Rich and Langer ( 11) suggested that changes in calcium permeability at the level of the glycocalyx or lipid bilayer were responsible. More recently Tunstall et al (12) provided evidence in fish and frog atria that calcium entry appeared to be through the sodium calcium exchanger. The experimental paradigm used in their studies demonstrated that contracture tension and abnormal action potentials returned to baseline after a period of calcium reperfusion, thus suggesting that membrane damage or leak was not responsible for the calcium entry.…”

Section: Discussionmentioning

confidence: 99%

“…In turn, the calcium overload is hypothesized to be an important determinant ofthe mechanical dysfunction seen during calcium reperfusion (3,4). The calcium overload and mechanical dysfunction may vary depending on a variety of experimental circumstances, and may be attenuated by a number of different interventions (9)(10)(11)(12). Although recent studies suggest that the principal mechanism for calcium entry may be through the sodium-calcium exchange transporter, there are no data examining the relationship between the driv-gradient, and the subsequent dysfunction (6,7,12).…”

Section: Introductionmentioning

confidence: 99%

“…Since increases in intracellular sodium content seem to be an important factor in the genesis of the calcium paradox, we used a series of blocking agents in experiments designed to ascertain whether sodium entry in this model was via sodiumcalcium exchange or through sodium or calcium channels, as has recently been suggested (12,22).…”

Section: Introductionmentioning

confidence: 99%

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Decrease in the transmembrane sodium activity gradient in ferret papillary muscle as a prerequisite to the calcium paradox.

Guarnieri

1988

J. Clin. Invest.

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Sodium-dependent calcium exchange may be an important mediator of calcium reperfusion damage during the calcium paradox phenomenon. We measured intracellular sodium activity with ion-selective electrodes during a 15-min period of calcium reperfusion in isolated ferret papillary muscles. During the calcium-free period, a Na' increased from 9.0±0.9 to 18.9±4.3 mM. With reinstitution of calcium there was a significant contracture. The amount of contracture after calcium reinstitution was related to sodium loading during the calcium-free period. We were unable to block sodium entry during the calcium-free period with either nitrendipine, tetrodotoxin, or low concentrations of amiloride. 10-3 M amiloride or lithium for sodium substitution in the calcium-free period, however, obliterated the increase in a Na' activity and the subsequent paradox. These data suggest that sodium loading is a necessary prerequisite for the calcium paradox and that one mechanism of sodium entry is through Na+/Ca2" exchange. Under these conditions, no increase in the rest force is seen without previous sodium gains, suggesting that sodium-dependent calcium exchange is an important trigger for the calcium reflow, the calcium paradox.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Decrease in the transmembrane sodium activity gradient in ferret papillary muscle as a prerequisite to the calcium paradox.

Guarnieri

1988

J. Clin. Invest.

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Molecular dissection of the myelinated axon

Waxman

Ritchie

1993

Annals of Neurology

326

202

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The membrane of the myelinated axon expresses a rich repertoire of physiologically active molecules: (1) Voltage-sensitive NA+ channels are clustered at high density (approximately 1,000/microns 2) in the nodal axon membrane and are present at lower density (< 25/microns 2) in the internodal axon membrane under the myelin. Na+ channels are also present within Schwann cell processes (in peripheral nerve) and perinodal astrocyte processes (in the central nervous system) which contact the Na+ channel-rich axon membrane at the node. In some demyelinated fibers, the bared (formerly internodal) axon membrane reorganizes and expresses a higher-than-normal Na+ channel density, providing a basis for restoration of conduction. The presence of glial cell processes, adjacent to foci of Na+ channels in immature and demyelinated axons, suggests that glial cells participate in the clustering of Na+ channels in the axon membrane. (2) "Fast" K+ channels, sensitive to 4-aminopyridine, are present in the paranodal or internodal axon membrane under the myelin; these channels may function to prevent reexcitation following action potentials, or participate in the generation of an internodal resting potential. (3) "Slow" K+ channels, sensitive to tetraethylammonium, are present in the nodal axon membrane and, in lower densities, in the internodal axon membrane; their activation produces a hyperpolarizing afterpotential which modulates repetitive firing. (4) The "inward rectifier" is activated by hyperpolarization. This channel is permeable to both Na+ and K+ ions and may modulate axonal excitability or participate in ionic reuptake following activity. (5) Na+/K(+)-ATPase and (6) Ca(2+)-ATPase are also present in the axon membrane and function to maintain transmembrane gradients of Na+, K+, and Ca2+. (7) A specialized antiporter molecule, the Na+/Ca2+ exchanger, is present in myelinated axons within central nervous system white matter. Following anoxia, the Na+/Ca2+ exchanger mediates an influx of Ca2+ which damages the axon. The molecular organization of the myelinated axon has important pathophysiological implications. Blockade of fast K+ channels and Na+/K(+)-ATPase improves action potential conduction in some demyelinated axons, and block of the Na+/Ca2+ exchanger protects white matter axons from anoxic injury. Modification of ion channels, pumps, and exchangers in myelinated fibers may thus provide an important therapeutic approach for a number of neurological disorders.

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Reperfusion paradox: A novel mode of glial cell injury

Kim-Lee

Stokes

Yates

1992

Glia

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We have attempted to reconstruct in vitro the events that may occur in vivo during reperfusion injury after ischemia in the central nervous system. The phenomenon is induced by previous exposure to low calcium solutions ("calcium paradox") before the reperfusion episode. Intracellular calcium alterations during reperfusion of human astrocytoma U1242MG cells have been investigated with microspectrofluorimetry using the calcium-sensitive dye fura-2. Cells were perfused in calcium-free buffer solution for 30 min and then re-exposed to the control buffer solution (1.5 mM CaCl2). [Ca2+]i increased up to 3.5 times control levels during the reperfusion period. The mechanism of the increase was also investigated. Addition of TTX (2 microM) or choline chloride sodium substitution during perfusion with low calcium prevented the [Ca2+]i increase during reperfusion. Reperfusion increases in [Ca2+]i were exacerbated by low potassium in the perfusion medium, but unaltered by the calcium channel blockers cadmium (100 microM) and nickel (100 microM). In a similar manner, flunarizine (10 microM) and cadmium (100 microM) were unable to modify reperfusion [Ca2+]i alterations. Low sodium in the reperfusion medium produced significant increases in [Ca2+]i if preceded by low potassium and calcium perfusion. The viability of cells after 24 h of incubation after the insult produced by exposure to Ca(2+)-free media for 30 min was also investigated. Compared with control groups, the groups treated with Ca(2+)-free media for 30 min had a decreased number of surviving cells and morphological alterations indicative of cell pathology. The relative number of cytotoxic cells was increased by maneuvers (low potassium perfusion) that presumably blocked the Na/KATPase.(ABSTRACT TRUNCATED AT 250 WORDS)

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Pathways for the movements of ions during calcium-free perfusion and the induction of the ‘calcium paradox’

Cited by 34 publications

References 60 publications

Decrease in the transmembrane sodium activity gradient in ferret papillary muscle as a prerequisite to the calcium paradox.

Decrease in the transmembrane sodium activity gradient in ferret papillary muscle as a prerequisite to the calcium paradox.

Molecular dissection of the myelinated axon

Reperfusion paradox: A novel mode of glial cell injury

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