Voltage-dependent K+ channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation. Some Kv channels participate in the proliferation and migration of normal and tumour cells, contributing to metastasis. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumours and cancer cells. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin’s lymphomas. However, Kv1.3 and Kv1.5 are similarly remodelled in some cancers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. Differential remodelling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumour growth and their importance as potential tumour markers. However, despite of this increasing body of information, which considers Kv1.3 and Kv1.5 as emerging tumoral markers, further research must be performed to reach any conclusion. In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer.

The trabecular meshwork tissue controls the drainage of the aqueous humor of the eye. A dysfunctional trabecular meshwork leads to an altered fluid resistance, which results in increased intraocular pressure (IOP). IOP is the major risk factor of glaucoma, the second‐leading cause of blindness in the developed world. In the search for genes altered by glaucomatous insults, we identified angiopoietin‐like7 (ANGPTL7), a member of the ANGPTL family. Although structurally related to the angiopoietins, ANGPTL7′s function is poorly understood. Because ANGPTL7 is secreted and because extracellular matrix (ECM) deposition and organization is critical for aqueous humor resistance, we investigated the effect of ANGPTL7 on relevant trabecular meshwork ECM genes and proteins. We find that overexpression of ANGPTL7 in primary human trabecular meshwork cells altered the expression of fibronectin, collagens type I, IV & V, myocilin, versican, and MMP1. ANGPTL7 also interfered with the fibrillar assembly of fibronectin. Finally, we find that silencing ANGPTL7 during the glucocorticoid insult significantly affected the expression of other steroid‐responsive proteins. These results indicate that ANGPTL7 modulates the trabecular meshwork’s ECM as well as the response of this tissue to steroids. Together with previous findings, these properties strengthen ANGPTL7′s candidacy for the regulation of IOP and glaucoma.

Voltage-dependent potassium (K_v) channels play a pivotal role in the modulation of macrophage physiology. Macrophages are professional antigen-presenting cells and produce inflammatory and immunoactive substances that modulate the immune response. Blockage of K_v channels by specific antagonists decreases macrophage cytokine production and inhibits proliferation. Numerous pharmacological agents exert their effects on specific target cells by modifying the activity of their plasma membrane ion channels. Investigation of the mechanisms involved in the regulation of potassium ion conduction is, therefore, essential to the understanding of potassium channel functions in the immune response to infection and inflammation. Here, we demonstrate that the biophysical properties of voltage-dependent K⁺ currents are modified upon activation or immunosuppression in macrophages. This regulation is in accordance with changes in the molecular characteristics of the heterotetrameric K_v1.3/K_v1.5 channels, which generate the main K_v in macrophages. An increase in K⁺ current amplitude in lipopolysaccharide-activated macrophages is characterized by a faster C-type inactivation, a greater percentage of cumulative inactivation, and a more effective margatoxin (MgTx) inhibition than control cells. These biophysical parameters are related to an increase in K_v1.3 subunits in the K_v1.3/K_v1.5 hybrid channel. In contrast, dexamethasone decreased the C-type inactivation, the cumulative inactivation, and the sensitivity to MgTx concomitantly with a decrease in K_v1.3 expression. Neither of these treatments apparently altered the expression of K_v1.5. Our results demonstrate that the immunomodulation of macrophages triggers molecular and biophysical consequences in K_v1.3/K_v1.5 hybrid channels by altering the subunit stoichiometry.

Trabecular meshwork (TM) cell shape, volume, contractility and their interactions with extracellular matrix determine outflow facility. Because cell volume seems essential to TM function, this study was conducted to investigate further the ionic channels and receptors involved in regulatory volume decrease and their roles in modulating outflow facility. Primary cultures of bovine TM cells were used. K(+) and Cl(-) currents were studied with whole-cell patch clamping. Swelling was induced by hypotonic shock. [Ca(2+)](i) was measured in TM cells loaded with fura-2. Bovine anterior segments were perfused at constant pressure to measure outflow facility. Hypotonic media activated both the high-conductance Ca(2+)-activated K(+) channel (BK(Ca)) and swelling-activated Cl(-) channel (Cl(swell)) currents and induced release of adenosine 5'-triphosphate (ATP) from TM cells. ATP activated P2Y(2) receptors with the following profile: ATP = uridine 5'-triphosphate (UTP) > adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma S) > adenosine 5'-diphosphate (ADP) = uridine 5'-diphosphate (UDP), and increased BK(Ca) current. Hypotonic medium initially decreased outflow facility in perfused anterior segments, which recovered with time to baseline levels. Addition of tamoxifen or iberiotoxin (Cl(swell) and BK(Ca) blockers, respectively) lengthened the recovery phase, which implies that these channels participate in cell volume regulation. In contrast, an activator of BK(Ca)s (NS1619) produced the opposite effect. Cell swelling activates a regulatory volume decrease mechanism that implies activation of K(+) and Cl(-) currents and participation of P2Y(2) receptors. Because previous studies have shown that intracellular volume of TM cells is an important determinant of outflow facility, it seems feasible that cell volume regulation would be part of the homeostatic mechanisms of the TM, to regulate the outflow pathway.