Magnesium-inhibited, non-selective cation current (I-MIC) is activated by depletion of intracellular Mg2+ and ATP. IMIC transports various divalent cations including Mg2+ and Ca2+, and is involved in cell viability. We investigated the effect of actin dynamics on ImIc. Formation of a stable cortical actin network by calyculin A inhibited the activation of I-MIC while the actin depolymerizing reagent, cytochalasin D, reversed the inhibition. Induction of a dense cortical actin layer by transfecting the constitutively active form of RhoA also inhibited the activation of I-MIC. These results suggest that the activation of ImIc may be dynamically regulated by actin cytoskeleton rearrangement. (c) 2005 Elsevier Inc. All rights reserved.