Electric stimulation of human fibroblasts causes an increase in Ca2+ influx and the exposure of additional insulin receptors

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Abstract
Previously we reported that treating human fibroblasts in cell culture with high-voltage, pulsed galvanic stimulation (HVPGS) can significantly increase cellular protein and DNA synthesis (Bourguignon and Bourguignon: FASEB J., 1:398–402, 1987). In this study we have identified two of the early cellular events which occur following exposure to HVPGS: (1) an increase in Ca2+ uptake from the external medium and (2) an increase in the number of insulin receptors on the fibroblast cell surface. The increase in Ca2+ uptake begins within the first minute of electric stimulation while increased insulin binding is not detected until the second minute of stimulation. The HVPGS-induced increase in insulin binding can be inhibited by bepridil, a specific Ca2+ channel blocker, suggesting that the Ca2+ influx is required for the exposure of additional insulin receptors on the cell surface. Furthermore, we have determined that the addition of insulin to electrically stimulated cultures results in (1) an immediate, second increase in Ca2+ uptake and (2) significant increases in both protein and DNA synthesis compared to cells which were not stimulated. All three of these insulin-dependent effects are also inhibited by bepridil. Based on these results, we propose that HVPGS initially triggers the opening of voltage-sensitive calcium channels in the fibroblast plasma membrane. The increased level of intracellular Ca2+ then induces the exposure of additional insulin receptors on the cell surface. If insulin is available to bind the additional receptors, the fibroblasts will significantly increase both protein and DNA synthesis.