Influence of Calcium on Regulatory Volume Decrease: Role of Potassium Channels

Abstract

In most cell types, hyposmotic swelling consistently elicits an increase in the concentration of cytosolic Ca²⁺ – [Ca²⁺]_i – with contributions of extracellular and intracellular sources. The mechanisms of Ca²⁺ entry and release from endogenous sources are not fully clarified and may be cell specific. The ubiquity of the swelling-evoked [Ca²⁺]_i rise makes Ca²⁺ a likely candidate for a role as osmotransducing signal. However, the regulatory volume decrease (RVD) which follows swelling and the osmolyte fluxes involved in this process are not always Ca²⁺ dependent. It was found that, with a few exceptions, in most cell types the osmosensitive Cl^– efflux pathway and the swelling-activated organic osmolyte fluxes are Ca²⁺ independent. In contrast, Ca²⁺-dependent or Ca²⁺-independent K⁺ fluxes activated by swelling are detected, depending on the cell type. The close correlation found in this review between the Ca²⁺ dependence of RVD and that of the K⁺ channels activated by swelling led to the conclusion that it is the type of osmosensitive K⁺ pathway which largely confers the Ca²⁺ dependence to RVD. Interestingly, this coincidence of Ca²⁺-dependent K⁺ efflux and RVD is found predominantly in epithelial cells, whereas in nonepithelial cells both processes are largely Ca²⁺ independent. In these cells, the [Ca²⁺]_i rise elicited by swelling may be an epiphenomenon.

Cell Volume Regulation in Response to Hypotonicity Is Impaired in HeLa Cells Expressing a Protein Kinase C α Mutant Lacking Kinase Activity

“…2 and Table I), suggesting that Ca 2ϩ release from intracellular stores via an IP 3 -dependent mechanism is critical for volume recovery in these cells. This conclusion is in agreement with results obtained in astrocytes where Ca 2ϩ mobilized from the endoplasmic reticulum was suggested to be the source of Ca 2ϩ required for hypotonicity-stimulated K ϩ release (37,40). In addition, swelling has been associated in a wide variety of cells with intracellular Ca 2ϩ increases that activate K ϩ and Cl Ϫ efflux via channels, loss of water, and as a consequence, recovery of cell volume (8,41 (Fig.…”

Volume changes and whole cell membrane currents activated during gradual osmolarity decrease in C6 glioma cells: contribution of two types of K+ channels

“…15). In epithelial cells hyposmolarity activates Ca 2ϩ -dependent K ϩ channels, whereas in most nonepithelial cells the volume-sensitive K ϩ channels are Ca 2ϩ independent (15). Interestingly, in the present work we found the operation of both Ca 2ϩ -dependent and Ca 2ϩ -independent K ϩ channels in the same cell type, which activate at different times and by different signals.…”

“…This type of channel appears similar to that involved in RVD in most epithelial cells (15). The Ca 2ϩ -independent channel, which is apparently also voltage independent, activates only by osmolarity and shows a pharmacological profile characterized by insensitivity to typical K ϩ channel blockers such as TEA, quinidine, 4-AP, and Ba 2ϩ but sensitivity to clofilium.…”

“…Volume-activated K ϩ channels show marked differences with respect to Ca 2ϩ dependence, depending on the cell type (reviewed in Ref. 15). In epithelial cells hyposmolarity activates Ca 2ϩ -dependent K ϩ channels, whereas in most nonepithelial cells the volume-sensitive K ϩ channels are Ca 2ϩ independent (15).…”

Hypotonic activation of volume-sensitive outwardly rectifying chloride channels in cultured PASMCs is modulated by SGK

“…Regulation of the water balance in mammalian cells is a complex process, which includes stringent control of the transmembrane traffic of ions other than Na ϩ (40). For example, hypotonic swelling of canine pulmonary artery smooth muscle cells (PASMCs) activates a volume-sensitive organic osmolyte and anion channel (VSOAC), characterized by a moderate outward rectification, and an anion permeability of I Ϫ Ͼ Cl Ϫ Ͼ aspartate (53).…”