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Effects of Pharmacological Modulators of Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> Channels on Proliferation of Human Dermal Fibroblast

Effects of Pharmacological Modulators of Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> Channels on Proliferation of Human Dermal Fibroblast

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Employing electrophysiological and cell proliferation assay techniques, we studied the effects of Ca<SUP>2&#8290;</SUP>- activated K<SUP>&#8290;</SUP> channel modulators on the proliferation of human dermal fibroblasts, which is important in wound healing. Macroscopic voltage-dependent outward K<SUP>&#8290;</SUP> currents were found at about &#8291;40 mV stepped from a holding potential of &#8291;70 mV. The amplitude of K<SUP>&#8290;</SUP> current was increased by NS1619, a specific large-conductance Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> (BK) channel activator, but decreased by iberiotoxin (IBTX), a specific BK channel inhibitor. To investigate the presence of an intermediate-conductance Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> (IK) channels, we pretreated the fibroblasts with low dose of TEA to block BK currents, and added 1-EBIO (an IK activator). 1-EBIO recovered the currents inhibited by TEA. When various Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> channel modulators were added into culture media for 1∼3 days, NS1619 or 1-EBIO inhibited the cell proliferation. On the other hand, IBTX, clotrimazole or apamin, a small conductance Ca<SUP>2&#8290;</SUP>-activated K<SUP>&#8290;</SUP> channel (SK) inhibitor, increased it. These results suggest that BK, IK, and SK channels might be involved in the proliferation of human dermal fibroblasts, which is inversely related to the channel activation.

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