Intermediate-conductance [Ca.sup.2+]-activated [K.sup.+] channels regulate human prostate cancer cell proliferation through a close control of calcium entry

Accumulating data point to [K.sup.+] channels as relevant players in controlling cell cycle progression and proliferation of human cancer cells, including prostate cancer (PCa) cells. However, the mechanisms) by which [K.sup.+] channels control PCa cell proliferation remain illusive. In this study, using the techniques of molecular biology, biochemistry, electrophysiology and calcium imaging, we studied the expression and functionality of intermediate-conductance calcium-activated potassium channels ([IK.sub.Ca1]) in human PCa as well as their involvement in cell proliferation. We showed that [IK.sub.Ca1] mRNA and protein were preferentially expressed in human PCa tissues, and inhibition of the [IK.sub.Ca1] potassium channel suppressed PCa cell proliferation. The activation of [IK.sub.Ca1] hyperpolarizes membrane potential and, by promoting the driving force for calcium, induces calcium entry through TRPV6, a cation channel of the TRP (Transient Receptor Potential) family. Thus, the overexpression of the [IK.sub.Ca1] channel is likely to promote carcinogenesis in human prostate tissue. doi:10.1038/onc.2009.25; published online 9 March 2009 Keywords: intermediate-conductance potassium channels; TRPV6; prostate cancer; proliferation; capacitative calcium entry; patch clamp