Kv1.3 and Kv1.5 are inhibited by 4-aminopyridine (4-AP) and tetraethylammonium (TEA), which are general K + channel blockers (Grissmer et al., 1994). Such a different biophysical features may explain their distinct regulation in a number of cell types. Unlike Kv1.3, Kv1.5 inactivation is slow and lacks cumulative inactivation. The conductance of the Kv1.5 channel is 8 pS, and the voltage required for activation is ~24 mV. Kv1.5 currents contribute to the ultra-rapid activating K + current in the heart known as I kur, which plays a role in the repolarization of an action potential (Lesage et al., 1992).

For example, Kv1.5 is expressed in the immune system, the kidney, skeletal and smooth muscle and, to a lesser extent, the brain (Coma et al., 2003 Vicente et al., 2003, 2006 Villalonga et al., 2008 Bielanska et al., 2012a, b). Similar to the Kv1.3 channel, Kv1.5 is also ubiquitously expressed (Swanson et al., 1990 Bielanska et al., 2009, 2010). In contrast, the Kv1.5 channel was first isolated from the human ventricle and is also expressed in the atria (Tamkun et al., 1991). The single channel conductance of Kv1.3 is 13 pS, and the voltage required for activation is в€’35 mV. Kv1.3 currents exhibit a characteristic cumulative inactivation and a marked C-type inactivation.

This channel is highly expressed in lymphocytes and the olfactory bulb (Stuhmer et al., 1989), and several studies have reported that it is also expressed in the hippocampus (Veh et al., 1995), epithelia (Grunnet et al., 2003), adipose tissue (Xu et al., 2004), and both skeletal, and smooth muscle (Villalonga et al., 2008 Bielanska et al., 2012a, b). Although Kv1.3 was first cloned from brain tissue, its expression is widely distributed throughout the body (Swanson et al., 1990 Bielanska et al., 2009, 2010). The voltage dependent K + channels Kv1.3 and Kv1.5 are members of the Shaker (Kv1) family of K + channels and are implicated in tissue differentiation and cell growth (Felipe et al., 2006). Given their pivotal role in cell physiology, abnormalities in Kv functions can lead to several channelopathies (Ashcroft, 2000). Accordingly, several studies have reported that Kv channels are involved in the activation, proliferation, differentiation, and migration of leukocytes (Cahalan and Chandy, 1997 Wulff et al., 2003 Panyi et al., 2004 Beeton et al., 2005 Felipe et al., 2006). Kv channels also control leukocyte membrane potential and play a role in immune system responses (Cahalan and Chandy, 2009). Kv channels also contribute to a wide variety of cellular processes including the maintenance of vascular smooth muscle tone (Yuan et al., 1998), cell growth (DeCoursey et al., 1984), the regulation of cell volume (Deutsch and Lee, 1988), adhesion (Itoh et al., 1995), mobility, epithelial transport (Kupper et al., 1995), homeostasis (Xu et al., 2003), insulin release (Xu et al., 2004), and apoptosis (Storey et al., 2003). Voltage-dependent K + channels (Kv), a superfamily comprised of 12 subfamilies (Kv1-Kv12), play a key role in the maintenance of resting membrane potential and the control of action potentials (Hille, 2001). Potassium channels are one of the most diverse and ubiquitous families of membrane proteins and are encoded by more than 75 different genes (Caterall et al., 2002). Voltage-dependent K + channels Kv1.3 and Kv1.5 In this review, we summarize what it has been lately documented about Kv1.3 and Kv1.5 channels in human cancer. 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. Differential remodeling of Kv1.3 and Kv1.5 expression in human cancers may indicate their role in tumor growth and their importance as potential tumor markers. For instance, expression of Kv1.3 and Kv1.5 correlates with a certain grade of tumorigenicity in muscle sarcomas. However, Kv1.3 and Kv1.5 are similarly remodeled in some cancers.

Interestingly, evidence indicates that Kv1.5 channel shows inversed correlation with malignancy in some gliomas and non-Hodgkin's lymphomas. In general, while the expression of Kv1.3 apparently exhibits no clear pattern, Kv1.5 is induced in many of the analyzed metastatic tissues. Altered expression of Kv1.3 and Kv1.5 channels has been found in several types of tumors and cancer cells. Some Kv channels participate in the proliferation and migration of normal and tumor cells, contributing to metastasis. Voltage-dependent K + channels (Kv) are involved in a number of physiological processes, including immunomodulation, cell volume regulation, apoptosis as well as differentiation.

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