Volume regulatory decrease in UMR-106.01 cells is mediated by specific α¹ subunits of L-type calcium channels

An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca²⁺]_i), which initiates regulatory volume decrease (RVD). The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca²⁺ influx. Herein is described the initiation of RVD in UMR-106.01 cells, mediated by hypotonically induced [Ca²⁺]_i transients resulting from the activation of specific isoforms of L-type Ca channels. The authors further demonstrate that substrate interaction determines which specific α₁ Ca channel subunit isoform predominates and mediates Ca²⁺ entry and RVD. Swelling-induced [Ca²⁺]_i transients, and RVD in cells grown on a type I collagen matrix, are inhibited by removal of Ca from extracellular solutions, dihydropyridines, and antisense oligodeoxynucleotides directed exclusively to the α_1C isoform of the L-type Ca channel. Ca²⁺ transients and RVD in cells grown on untreated glass cover slips were inhibited by similar maneuvers, but only by antisense oligodeoxynucleotides directed to the α_1S isoform of the L-type Ca channel. This represents the first molecular identification of the Ca channels that transduce the initiation signal for RVD by osteoblastic cells.