Predominant expression of Kv1.3 voltage-gated K+ channel subunit in rat prostate cancer cell lines: electrophysiological, pharmacological and molecular characterisation

Abstract

Voltage-gated K+ currents expressed in two rat prostate cancer ("Dunning") cell lines of markedly different metastatic ability were characterised using electrophysiological, pharmacological and molecular approaches. Whole-cell patch-clamp recordings showed that both strongly metastatic MAT-LyLu and weakly metastatic AT-2 cell lines possessed outward (delayed-rectifier type) K+ currents, which activated at around -40 mV. From the parameters measured, several characteristics of the two cell lines were similar. However, a number of statistically significant differences were noted for MAT-LyLu versus the AT-2 cells as follows: (1) current densities were smaller; (2) the slope factor for channel activation was smaller; (3) the voltage at which current was half-inactivated, and the slope factor for channel inactivation were greater; (4) the time constants for current decay at -20 and 0 mV were smaller; and (5) the residual peak current was larger following 60 s of repetitive voltage pulses for stimulation frequencies in the range 0.05-0.2 Hz. On the other hand, the K+ currents in both cell lines showed similar pharmacological profiles. Thus, the currents were blocked by 4-aminopyridine, tetraethylammonium, verapamil, margatoxin, and charybdotoxin, with highly similar IC(50)s for given blockers. The electrophysiological and pharmacological data taken together suggested expression of voltage-gated K+ channels of the Kv1 family, expression of the Kv1.3 subunit being predominant. Western blot and RT-PCR tests both confirmed that the cells indeed expressed Kv1.3 and to a lesser extent Kv1.4 and Kv1.6 channel alpha-subunits. In view of the similarity of channel expression in the two cell lines, voltage-gated K+ channel activity may not be a primary determinant of metastatic potential in the rat model of prostate cancer, but the possible contribution of K+ channel activity to the metastatic process is discussed.

Voltage-gated potassium channel EAG2 controls mitotic entry and tumor growth in medulloblastoma via regulating cell volume dynamics

“…1A). The expression levels of several other potassium channels previously shown to be up-regulated in cancers were either significantly decreased (TASK3 [Mu et al 2003], BK [Liu et al 2002;Bloch et al 2007], GIRK1 [Stringer et al 2001]) or unchanged (Kv1.3 [Fraser et al 2003]) ( Fig. 1A; Supplemental Fig.…”

Blockage of intermediate-conductance-Ca2+-activated K+ channels inhibits progression of human endometrial cancer

“…Ion channels, including K þ channels, are important for cell cycle and cell proliferation and are found in a variety of cancer cells (Nilius and Wohlrab, 1992;Skryma et al, 1997;Ouadid-Ahidouch et al, 2000;Fraser et al, 2003;Parihar et al, 2003;Farias et al, 2004;Jager et al, 2004). It has been shown that K þ channels play a role in controlling proliferation and transformation of epithelial cells (Pardo et al, 1999).…”

Ion channels in death and differentiation of prostate cancer cells

“…Facilitation of K þ efflux by K þ -channel openers, (minoxidil, 1-ethyl-2-benzimidazolinone (EBIO), or diazoxide) was able to increase growth of PC-3 cells by 30-50%, whereas K þ -channel inhibitors (dequalinium, amiodarone, and glibenclamide) caused a dosedependent, growth inhibition of both androgen-sensitive (LNCaP, MDA-PCA-2B) and androgen-insensitive (PC-3, DU-145) human PCa cell lines. 15 The same blockers induced PC-3 apoptosis within 4 h treatment. 15 Thus, we can conclude that PCa epithelial cells that preserve androgen sensitivity, and display relatively weak metastatic potential, are generally characterized by higher I K and K þ -channel expression.…”

“…The existing data suggests that K v 1.3 is the dominant K vclass channel expressed in normal and cancerous rat and human prostate tissues, as well as in prostatic cell lines with different metastatic potentials, with lesser contributions from K v 1.4 and K v 1.6. [14][15][16] The difference between strongly metastatic rat MAT-LyLu and weakly metastatic AT-2 cell lines was again mostly found with regard to I K density, rather than biophysical properties. 16 This is consistent with the altered expression of the same channel types as opposed to the appearance of new ones.…”