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Am J Physiol Regul Integr Comp Physiol 2003 Mar 6; [epub ahead of print]

Ca2+ uptake and cellular integrity in rat EDL muscle exposed to electrostimulation, electroporation or A23187.

Gissel H, Clausen T.

Department of Physiology, University of Aarhus, DK-8000 Aarhus C, Denmark.

We tested the hypothesis that increased Ca(2+) uptake in rat extensor digitorum longus (EDL) muscle elicits cell membrane damage as assessed from the release of the intracellular enzyme lactate dehydrogenase (LDH). This was done using 1) electrical stimulation, 2) electroporation, and 3) a Ca(2+) ionophore A23187. Continuous stimulation at 1 Hz for 120-240 min caused an increase in (45)Ca uptake, which was closely correlated to LDH release. This LDH release increased markedly with temperature. After 120 min of electrical stimulation at 1 Hz, resting (45)Ca uptake was increased 5.6-fold compared with unstimulated muscles. This was associated with an 8-fold increase in LDH leakage, an effect that was halved by lowering [Ca(2+)]o. The post-stimulatory increase in resting (45)Ca uptake persisted for at least 120 min. An acute increase in sarcolemma leakiness induced by electroporation markedly increased (45)Ca uptake and LDH leakage. Both effects depended on [Ca(2+)]o. The Ca(2+) ionophore A23187 increased (45)Ca uptake but caused no rise in tension. Concomitantly, LDH leakage increased 18-fold within 30 min, an effect that was abolished by omitting Ca(2+) from the buffer. We conclude that increased Ca(2+) influx may be an important cause of cell membrane damage arising during and after exercise or electrical shocks. Since membrane damage allows further influx of Ca(2+), this results in positive feedback that may further increase membrane degeneration.

PMID: 12623773

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